Breast Cancer

In patients with node-positive and locally advanced breast cancer (BC), postmastectomy radiation therapy (PMRT) decreases risk for recurrence and improves survival (Mutter et al). Proton therapy is an attractive newer way to deliver PMRT compared with photon-based methods and allows improved sparing of cardiopulmonary and other normal tissue. The phase 2 MC1631 trial included 82 patients with BC who underwent mastectomy with or without immediate breast reconstruction and who were randomly assigned to receive either conventional fractionated (50 Gy in 25 fractions of 2 Gy) or hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) proton PMRT. At a median follow-up of 39.3 months, both conventional fractionated and hypofractionated proton PMRT had similar complication rates (15% vs 20%; absolute difference 4.9%; one-sided 95% CI 18.5; P = .27), with most complications occurring in patients with immediate expander or implant-based reconstruction. Noninferiority of the hypofractionation group could not be determined after a median follow-up of 39 months. However, no isolated local regional recurrences in either treatment arm were seen. This study provides the first prospective, randomized data of hypofractionated proton PMRT. Further data are awaited to support this approach. 

In patients with metastatic hormone receptor (HR)–positive, PIK3CA-mutant BC, the combination of fulvestrant with alpelisib improves progression-free survival per the SOLAR-1 study.1 Higher rates of hyperglycemia observed among patients treated with alpelisib have led to alpelisib dose reductions, treatment delays, and discontinuation of the drug. In a retrospective cohort study of 247 patients with metastatic BC who received alpelisib either as standard care (n = 147) or in a clinical trial setting (n = 100), 61.5% of patients developed any-grade hyperglycemia (Shen et al). The rate of hyperglycemia was considerably higher in patients who received alpelisib as part of standard care vs clinical trial (80.3% vs 34.0%). Baseline body mass index ≥ 25 (P = .036) and A1c levels in the prediabetes and diabetes range were significantly associated with the development of any-grade hyperglycemia (P = .036 and P < .001, respectively) and grade 3-4 hyperglycemia (P < .001 for both). A total of 4.5% of patients discontinued alpelisib owing to hyperglycemia, 17% of patients required dose reductions, and in 27% of patients alpelisib was held until resolution of hyperglycemia. This study highlights the importance of the management of comorbidities before alpelisib treatment to ensure lower rates of adverse events. 

Patritumab deruxtecan (HER3-DXd) is a novel HER3-targeted antibody-drug conjugate that is being evaluated in HER3-expressing metastatic BC. The U31402-A-J101 study is a phase 1/2 trial including 182 heavily pretreated patients (median of five prior therapies) with HER3-expressing advanced BC who received HER3-DXd (Krop et al). The objective response rate was 30.1% (95% CI 21.8%-39.4%) in HR-positive, human epidermal growth factor receptor 2 (HER2)–negative BC, 22.6% (95% CI 12.3%-36.2%) in triple-negative BC, and 42.9% (95% CI 17.1%-71.1%) in HER2-positive BC. Although 71.4% of patients reported grade ≥ 3 treatment-emergent adverse events (TEAE), the overall rate of treatment discontinuation due to TEAE was low (9.9%). These findings demonstrate an encouraging efficacy and a manageable safety profile for patritumab deruxtecan in previously treated patients with BC across all subtypes. Further studies are awaited to confirm these findings and whether prior treatment with antibody-drug conjugate will affect the activity of this drug.

A retrospective analysis of a cohort including 149 patients with metastatic BC looked at predictors of prognosis in patients who had brain metastases and underwent stereotactic radiosurgery (Depner et al). The median overall survival was 14.8 months for the entire cohort. Receptor profiles and the presence of extracranial visceral metastases were significant predictors of prognosis. Overall survival outcomes worsened in patients with estrogen receptor (ER)–negative, HER2-negative BC (hazard ratio 2.00; 95% CI 1.09-3.67) but were better in those with ER-positive, HER2-positive BC (hazard ratio 0.43; 95% CI 0.19-0.96). Furthermore, the presence of extracranial visceral metastases was associated with poor survival outcomes (hazard ratio 2.90; 95% CI 1.53-5.50)

Additional Reference
1.    André F et al, for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940. doi: 10.1056/NEJMoa1813904
 

In patients with node-positive and locally advanced breast cancer (BC), postmastectomy radiation therapy (PMRT) decreases risk for recurrence and improves survival (Mutter et al). Proton therapy is an attractive newer way to deliver PMRT compared with photon-based methods and allows improved sparing of cardiopulmonary and other normal tissue. The phase 2 MC1631 trial included 82 patients with BC who underwent mastectomy with or without immediate breast reconstruction and who were randomly assigned to receive either conventional fractionated (50 Gy in 25 fractions of 2 Gy) or hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) proton PMRT. At a median follow-up of 39.3 months, both conventional fractionated and hypofractionated proton PMRT had similar complication rates (15% vs 20%; absolute difference 4.9%; one-sided 95% CI 18.5; P = .27), with most complications occurring in patients with immediate expander or implant-based reconstruction. Noninferiority of the hypofractionation group could not be determined after a median follow-up of 39 months. However, no isolated local regional recurrences in either treatment arm were seen. This study provides the first prospective, randomized data of hypofractionated proton PMRT. Further data are awaited to support this approach. 

In patients with metastatic hormone receptor (HR)–positive, PIK3CA-mutant BC, the combination of fulvestrant with alpelisib improves progression-free survival per the SOLAR-1 study.1 Higher rates of hyperglycemia observed among patients treated with alpelisib have led to alpelisib dose reductions, treatment delays, and discontinuation of the drug. In a retrospective cohort study of 247 patients with metastatic BC who received alpelisib either as standard care (n = 147) or in a clinical trial setting (n = 100), 61.5% of patients developed any-grade hyperglycemia (Shen et al). The rate of hyperglycemia was considerably higher in patients who received alpelisib as part of standard care vs clinical trial (80.3% vs 34.0%). Baseline body mass index ≥ 25 (P = .036) and A1c levels in the prediabetes and diabetes range were significantly associated with the development of any-grade hyperglycemia (P = .036 and P < .001, respectively) and grade 3-4 hyperglycemia (P < .001 for both). A total of 4.5% of patients discontinued alpelisib owing to hyperglycemia, 17% of patients required dose reductions, and in 27% of patients alpelisib was held until resolution of hyperglycemia. This study highlights the importance of the management of comorbidities before alpelisib treatment to ensure lower rates of adverse events. 

Patritumab deruxtecan (HER3-DXd) is a novel HER3-targeted antibody-drug conjugate that is being evaluated in HER3-expressing metastatic BC. The U31402-A-J101 study is a phase 1/2 trial including 182 heavily pretreated patients (median of five prior therapies) with HER3-expressing advanced BC who received HER3-DXd (Krop et al). The objective response rate was 30.1% (95% CI 21.8%-39.4%) in HR-positive, human epidermal growth factor receptor 2 (HER2)–negative BC, 22.6% (95% CI 12.3%-36.2%) in triple-negative BC, and 42.9% (95% CI 17.1%-71.1%) in HER2-positive BC. Although 71.4% of patients reported grade ≥ 3 treatment-emergent adverse events (TEAE), the overall rate of treatment discontinuation due to TEAE was low (9.9%). These findings demonstrate an encouraging efficacy and a manageable safety profile for patritumab deruxtecan in previously treated patients with BC across all subtypes. Further studies are awaited to confirm these findings and whether prior treatment with antibody-drug conjugate will affect the activity of this drug.

A retrospective analysis of a cohort including 149 patients with metastatic BC looked at predictors of prognosis in patients who had brain metastases and underwent stereotactic radiosurgery (Depner et al). The median overall survival was 14.8 months for the entire cohort. Receptor profiles and the presence of extracranial visceral metastases were significant predictors of prognosis. Overall survival outcomes worsened in patients with estrogen receptor (ER)–negative, HER2-negative BC (hazard ratio 2.00; 95% CI 1.09-3.67) but were better in those with ER-positive, HER2-positive BC (hazard ratio 0.43; 95% CI 0.19-0.96). Furthermore, the presence of extracranial visceral metastases was associated with poor survival outcomes (hazard ratio 2.90; 95% CI 1.53-5.50)

Additional Reference
1.    André F et al, for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940. doi: 10.1056/NEJMoa1813904
 

In patients with node-positive and locally advanced breast cancer (BC), postmastectomy radiation therapy (PMRT) decreases risk for recurrence and improves survival (Mutter et al). Proton therapy is an attractive newer way to deliver PMRT compared with photon-based methods and allows improved sparing of cardiopulmonary and other normal tissue. The phase 2 MC1631 trial included 82 patients with BC who underwent mastectomy with or without immediate breast reconstruction and who were randomly assigned to receive either conventional fractionated (50 Gy in 25 fractions of 2 Gy) or hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) proton PMRT. At a median follow-up of 39.3 months, both conventional fractionated and hypofractionated proton PMRT had similar complication rates (15% vs 20%; absolute difference 4.9%; one-sided 95% CI 18.5; P = .27), with most complications occurring in patients with immediate expander or implant-based reconstruction. Noninferiority of the hypofractionation group could not be determined after a median follow-up of 39 months. However, no isolated local regional recurrences in either treatment arm were seen. This study provides the first prospective, randomized data of hypofractionated proton PMRT. Further data are awaited to support this approach. 

In patients with metastatic hormone receptor (HR)–positive, PIK3CA-mutant BC, the combination of fulvestrant with alpelisib improves progression-free survival per the SOLAR-1 study.1 Higher rates of hyperglycemia observed among patients treated with alpelisib have led to alpelisib dose reductions, treatment delays, and discontinuation of the drug. In a retrospective cohort study of 247 patients with metastatic BC who received alpelisib either as standard care (n = 147) or in a clinical trial setting (n = 100), 61.5% of patients developed any-grade hyperglycemia (Shen et al). The rate of hyperglycemia was considerably higher in patients who received alpelisib as part of standard care vs clinical trial (80.3% vs 34.0%). Baseline body mass index ≥ 25 (P = .036) and A1c levels in the prediabetes and diabetes range were significantly associated with the development of any-grade hyperglycemia (P = .036 and P < .001, respectively) and grade 3-4 hyperglycemia (P < .001 for both). A total of 4.5% of patients discontinued alpelisib owing to hyperglycemia, 17% of patients required dose reductions, and in 27% of patients alpelisib was held until resolution of hyperglycemia. This study highlights the importance of the management of comorbidities before alpelisib treatment to ensure lower rates of adverse events. 

Patritumab deruxtecan (HER3-DXd) is a novel HER3-targeted antibody-drug conjugate that is being evaluated in HER3-expressing metastatic BC. The U31402-A-J101 study is a phase 1/2 trial including 182 heavily pretreated patients (median of five prior therapies) with HER3-expressing advanced BC who received HER3-DXd (Krop et al). The objective response rate was 30.1% (95% CI 21.8%-39.4%) in HR-positive, human epidermal growth factor receptor 2 (HER2)–negative BC, 22.6% (95% CI 12.3%-36.2%) in triple-negative BC, and 42.9% (95% CI 17.1%-71.1%) in HER2-positive BC. Although 71.4% of patients reported grade ≥ 3 treatment-emergent adverse events (TEAE), the overall rate of treatment discontinuation due to TEAE was low (9.9%). These findings demonstrate an encouraging efficacy and a manageable safety profile for patritumab deruxtecan in previously treated patients with BC across all subtypes. Further studies are awaited to confirm these findings and whether prior treatment with antibody-drug conjugate will affect the activity of this drug.

A retrospective analysis of a cohort including 149 patients with metastatic BC looked at predictors of prognosis in patients who had brain metastases and underwent stereotactic radiosurgery (Depner et al). The median overall survival was 14.8 months for the entire cohort. Receptor profiles and the presence of extracranial visceral metastases were significant predictors of prognosis. Overall survival outcomes worsened in patients with estrogen receptor (ER)–negative, HER2-negative BC (hazard ratio 2.00; 95% CI 1.09-3.67) but were better in those with ER-positive, HER2-positive BC (hazard ratio 0.43; 95% CI 0.19-0.96). Furthermore, the presence of extracranial visceral metastases was associated with poor survival outcomes (hazard ratio 2.90; 95% CI 1.53-5.50)

Additional Reference
1.    André F et al, for the SOLAR-1 Study Group. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929-1940. doi: 10.1056/NEJMoa1813904
 

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

Hormone receptor–positive breast cancer is the most common subtype, with established risk factors including exposure to exogenous hormones, reproductive history, and lifestyle components (alcohol intake, obesity). There are also less-recognized environmental influences that may disrupt endocrine pathways and, as a result, affect tumor development. Fine particulate matter (PM_2.5), produced by combustion processes (vehicles, industrial facilities), burning wood, and fires, among other sources, is composed of various airborne pollutants (metals, organic compounds, ammonium, nitrate, ozone, sulfate, etc.). Prior studies evaluating the association of PM_2.5 and breast cancer development have shown mixed results.^3,4 A prospective US cohort study including 196,905 women without a prior history of breast cancer estimated historical annual average PM_2.5 concentrations between 1980 and 1984 (10 years prior to enrollment) (White et al). A total of 15,870 breast cancer cases were identified, and a 10 μg/m³ increase in PM_2.5 was associated with an 8% increase in overall breast cancer incidence (HR 1.08; 95% CI 1.02-1.13). The association was observed for estrogen-receptor (ER)-positive (HR 1.10; 95% CI 1.04-1.17) but not ER-negative tumors. Future studies focusing on historic exposures, investigating geographic differences and the resultant effect on cancer development, are of interest.

HER2CLIMB was a pivotal phase 3 randomized, double-blinded trial that demonstrated significant improvement in survival outcomes with the combination of tucatinib/trastuzumab/capecitabine vs tucatinib/trastuzumab/placebo among patients with previously treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer.⁵ Real-world data help inform our daily practice because patients enrolled in clinical trials do not always accurately represent the general population. A retrospective cohort study including 3449 patients with HER2-positive metastatic breast cancer evaluated outcomes with tucatinib in a real-world setting, demonstrating results similar to those seen in HER2CLIMB. Among all patients who received tucatinib (n = 216), median real-world time to treatment discontinuation was 6.5 months (95% CI 5.4-8.8), median real-world time to next treatment (which can serve as a proxy for progression-free survival) was 8.7 months (95% CI 6.8-10.7), and real-world overall survival was 26.6 months (95% CI 20.2–not reached). Median real-world time to treatment discontinuation was 8.1 months (95% CI 5.7-9.5) for patients who received the approved tucatinib triplet combination after one or more HER2-directed regimens in the metastatic setting and 9.4 months (95% CI 6.3-14.1) for those receiving it in the second- or third-line setting (Kaufman et al). These results support the efficacy of tucatinib in a real-world population, suggesting that earlier use (second or third line) may result in better outcomes. Future studies will continue to address the positioning of tucatinib in the treatment algorithm for HER2-positive metastatic breast cancer, including the evaluation of novel combinations.

Additional References

1. Giuliano AE et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: The ACOSOG Z0011 (Alliance) randomized clinical trial. JAMA. 2017;318:918-926. doi: 10.1001/jama.2017.11470 
2. Bartels SAL, Donker M, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer: 10-year results of the randomized controlled EORTC 10981-22023 AMAROS Trial. J Clin Oncol. 2023;41:2159-2165. doi: 10.1200/JCO.22.01565
3. Gabet S, Lemarchand C, Guénel P, Slama R. Breast cancer risk in association with atmospheric pollution exposure: A meta-analysis of effect estimates followed by a health impact assessment. Environ Health Perspect. 2021;129:57012. doi: 10.1289/EHP8419
4. Hvidtfeldt UA et al. Breast cancer incidence in relation to long-term low-level exposure to air pollution in the ELAPSE pooled cohort. Cancer Epidemiol Biomarkers Prev. 2023;32:105-113. doi: 10.1158/1055-9965.EPI-22-0720  
5. Murthy RK et al. Tucatinib, trastuzumab, and capecitabine for HER2-positive metastatic breast cancer. N Engl J Med. 2020;382:597-609. doi:10.1056/NEJMoa1914609

The investigational anti-body drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) was associated with both improved progression-free survival and better safety than standard chemotherapy for patients with metastatic HER-2 negative (HR+/HER2–) breast cancer resistant to endocrine therapy, data from the phase 3 TROPION-Breast01 trial showed.

At a median follow-up of 10.8 months, the median progression-free survival (PFS) was 6.9 months for patients randomly assigned to receive Dato-DXd, compared with 4.9 months for the investigator’s choice of chemotherapy with either eribulin mesylate, vinorelbine, capecitabine, or gemcitabine. This difference translated into a 37% reduction in risk of disease progression with the ADC, reported Aditya Bardia, MD, MPH, director of the breast cancer research program at the Mass General Cancer Center in Boston.

Patients who received Dato-DXd had less than half the number of grade 3 or greater toxicities and fewer dose reductions or interruptions than patients who received chemotherapy, he noted in an oral abstract session at the 2023 European Society for Medical Oncology Congress.

“Overall, results support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor–positive breast cancer,” he said.
 

Different ADC, same target

Dr. Bardia noted that there is an unmet need for effective therapies for patients with metastatic HR+/HER2– breast cancer who experience disease progression after endocrine therapy and at least one line of systemic therapy.

Although chemotherapy is widely used in this population, it’s associated with low response rates, poor prognosis, and significant toxicities, including hematologic and neurologic adverse events (AEs).

Dato-DXd is composed of a monoclonal antibody targeting TROP2, a transmembrane glycoprotein overexpressed in cancer cells, linked to the topoisomerase 1 inhibitor deruxtecan as the toxic payload.

Dr. Bardia explained that Dato-DXd has four properties that distinguish it from other TROP2-directed ADCs: an optimized drug to antibody ratio of 4, a stable linker-payload, tumor-selective cleavable linker, both of which reduce off-target toxicities, and a bystander antitumor effect that can target TROP2-expressing cells in the tumor microenvironment.

In the phase I TROPION-PanTumor01 trial, Dato-DXd had promising anti-tumor activity and a manageable safety profile in patients with metastatic HR+/HER2– breast cancer, paving the way for the TROPION-Breast01 study reported here.
 

Efficacy results

In the Breast01 trial, 732 patients with inoperable or metastatic HR+/HER2– breast cancer previously treated with 1 or 2 lines of chemotherapy that had progressed on endocrine therapy were stratified by number of prior chemotherapy lines, geographic region, and prior CDK4/6 inhibitor status, and then randomized to either Dato-DXd 6 mg/kg intravenously on day 1 of each 3-week cycle (365 patients) or to investigator’s choice of chemotherapy (367 patients). According to the protocol, chemotherapy could be eribulin mesylate, vinorelbine, or gemcitabine delivered via IV on days 1 and 8 every 3 weeks, or oral capecitabine on days 1 through 14 of every 3-week cycle.

At the time of data cutoff, 93 patients assigned to the ADC and 39 assigned to chemotherapy were still on treatment.

As noted before, median PFS by blinded independent central review, one of two primary endpoints, was 6.9 months with Dato-DXd, compared with 4.9 months with chemotherapy, translating into a hazard ratio for progression of 0.63 (P < .0001)­­­.

The benefit was seen across nearly all subgroups except among patients who had not previously received a CDK4/6 inhibitor, and patients who had received a prior anthracycline but not a taxane.­

Objective response rates (ORR) were 36.4% with Dato-DXd (99.5% partial and .5% complete response), compared with 22.9% with chemotherapy (all partial responses; P values not reported).

Overall survival data, the other primary endpoint, were not mature at a median OS follow-up of 9.7 months, and will be reported at a later date.
 

­Safety results

“In terms of safety, the rate of grade 3 or higher treatment-related AEs in the Dato-DXd arm was less as compared to investigator choice of chemotherapy. This is a bit different from most of the studies; in general we see that the rate of adverse events is higher in the intervention arm as compared to the control arm,” Dr. Bardia commented.

Rates of dose reductions and dose interruptions due to treatment-related AEs were also lower with the ADC.

There were no patient deaths associated with Dato-DXd. One patient assigned to chemotherapy died from a complication associated with febrile neutropenia.

Most treatment-related AEs occurring in 15% of patients and AEs of special interest were of grade 1 and manageable.

The most common toxicities seen with the ADC were oral mucositis and dry eye. The most common side effects with chemotherapy were neutropenia and anemia, “the usual side effects you would expect with chemotherapy,” Dr. Bardia said, pointing out that the rate of grade 3 neutropenia was 31% with standard chemotherapy, compared with 1% with Dato-DXd.
 

Good, but we can do better

ESMO invited discussant Sarat Chandarlapaty, MD, PhD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York, commented that while the trial data showed superior efficacy and safety with Dato-DXd, compared with standard chemotherapy, it’s still unclear how it and other ADCs on the market and in the research pipeline may be used in therapy for this patient population.

“Would I rather prescribe Dato-DXd or more chemo after 1 to 2 lines of chemo in unselected HR-positive, HER2-negative breast cancer? The answer is Dato-DXd, but it leaves several unanswered questions for us,” he said.

“First, we have two ADCs approved in HR-positive breast cancer: another TROP2 ADC sacituzumab [govitecan] and a HER2 ADC trastuzumab deruxtecan. Would I rather give Dato over one of these? I don’t have an answer,” he added.

In addition, it’s unknown whether these drugs, which have the same topoisomerase-targeted payload, could be given in sequence, and there are as yet no clear answers as to whether patients might do better with Dato-DXd or with a PIK3ca inhibitor.

“I would say that the elephant in the room is really another question, and that is, ‘Is Dato-DXd in this context delivering on the promise of an ADC?’ ” Dr. Chandarlapaty said.

“I think translational research is urgently needed if we’re ultimately to deliver on the promise of these agents in the clinic,” he concluded.

The TROPION-Breast01 study is sponsored AstraZeneca, which is collaborating with Daiichi-Sankyo on global development and commercialization of Dato-DXd. Dr. Bardia disclosed advisory board activities and institutional research funding from AstraZeneca and Daiichi-Sankyo and others. Dr. Chandarlapaty disclosed research funding from both companies, and advisory board activities for AstraZeneca and others.

The investigational anti-body drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) was associated with both improved progression-free survival and better safety than standard chemotherapy for patients with metastatic HER-2 negative (HR+/HER2–) breast cancer resistant to endocrine therapy, data from the phase 3 TROPION-Breast01 trial showed.

At a median follow-up of 10.8 months, the median progression-free survival (PFS) was 6.9 months for patients randomly assigned to receive Dato-DXd, compared with 4.9 months for the investigator’s choice of chemotherapy with either eribulin mesylate, vinorelbine, capecitabine, or gemcitabine. This difference translated into a 37% reduction in risk of disease progression with the ADC, reported Aditya Bardia, MD, MPH, director of the breast cancer research program at the Mass General Cancer Center in Boston.

Patients who received Dato-DXd had less than half the number of grade 3 or greater toxicities and fewer dose reductions or interruptions than patients who received chemotherapy, he noted in an oral abstract session at the 2023 European Society for Medical Oncology Congress.

“Overall, results support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor–positive breast cancer,” he said.
 

Different ADC, same target

Dr. Bardia noted that there is an unmet need for effective therapies for patients with metastatic HR+/HER2– breast cancer who experience disease progression after endocrine therapy and at least one line of systemic therapy.

Although chemotherapy is widely used in this population, it’s associated with low response rates, poor prognosis, and significant toxicities, including hematologic and neurologic adverse events (AEs).

Dato-DXd is composed of a monoclonal antibody targeting TROP2, a transmembrane glycoprotein overexpressed in cancer cells, linked to the topoisomerase 1 inhibitor deruxtecan as the toxic payload.

Dr. Bardia explained that Dato-DXd has four properties that distinguish it from other TROP2-directed ADCs: an optimized drug to antibody ratio of 4, a stable linker-payload, tumor-selective cleavable linker, both of which reduce off-target toxicities, and a bystander antitumor effect that can target TROP2-expressing cells in the tumor microenvironment.

In the phase I TROPION-PanTumor01 trial, Dato-DXd had promising anti-tumor activity and a manageable safety profile in patients with metastatic HR+/HER2– breast cancer, paving the way for the TROPION-Breast01 study reported here.
 

Efficacy results

In the Breast01 trial, 732 patients with inoperable or metastatic HR+/HER2– breast cancer previously treated with 1 or 2 lines of chemotherapy that had progressed on endocrine therapy were stratified by number of prior chemotherapy lines, geographic region, and prior CDK4/6 inhibitor status, and then randomized to either Dato-DXd 6 mg/kg intravenously on day 1 of each 3-week cycle (365 patients) or to investigator’s choice of chemotherapy (367 patients). According to the protocol, chemotherapy could be eribulin mesylate, vinorelbine, or gemcitabine delivered via IV on days 1 and 8 every 3 weeks, or oral capecitabine on days 1 through 14 of every 3-week cycle.

At the time of data cutoff, 93 patients assigned to the ADC and 39 assigned to chemotherapy were still on treatment.

As noted before, median PFS by blinded independent central review, one of two primary endpoints, was 6.9 months with Dato-DXd, compared with 4.9 months with chemotherapy, translating into a hazard ratio for progression of 0.63 (P < .0001)­­­.

The benefit was seen across nearly all subgroups except among patients who had not previously received a CDK4/6 inhibitor, and patients who had received a prior anthracycline but not a taxane.­

Objective response rates (ORR) were 36.4% with Dato-DXd (99.5% partial and .5% complete response), compared with 22.9% with chemotherapy (all partial responses; P values not reported).

Overall survival data, the other primary endpoint, were not mature at a median OS follow-up of 9.7 months, and will be reported at a later date.
 

­Safety results

“In terms of safety, the rate of grade 3 or higher treatment-related AEs in the Dato-DXd arm was less as compared to investigator choice of chemotherapy. This is a bit different from most of the studies; in general we see that the rate of adverse events is higher in the intervention arm as compared to the control arm,” Dr. Bardia commented.

Rates of dose reductions and dose interruptions due to treatment-related AEs were also lower with the ADC.

There were no patient deaths associated with Dato-DXd. One patient assigned to chemotherapy died from a complication associated with febrile neutropenia.

Most treatment-related AEs occurring in 15% of patients and AEs of special interest were of grade 1 and manageable.

The most common toxicities seen with the ADC were oral mucositis and dry eye. The most common side effects with chemotherapy were neutropenia and anemia, “the usual side effects you would expect with chemotherapy,” Dr. Bardia said, pointing out that the rate of grade 3 neutropenia was 31% with standard chemotherapy, compared with 1% with Dato-DXd.
 

Good, but we can do better

ESMO invited discussant Sarat Chandarlapaty, MD, PhD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York, commented that while the trial data showed superior efficacy and safety with Dato-DXd, compared with standard chemotherapy, it’s still unclear how it and other ADCs on the market and in the research pipeline may be used in therapy for this patient population.

“Would I rather prescribe Dato-DXd or more chemo after 1 to 2 lines of chemo in unselected HR-positive, HER2-negative breast cancer? The answer is Dato-DXd, but it leaves several unanswered questions for us,” he said.

“First, we have two ADCs approved in HR-positive breast cancer: another TROP2 ADC sacituzumab [govitecan] and a HER2 ADC trastuzumab deruxtecan. Would I rather give Dato over one of these? I don’t have an answer,” he added.

In addition, it’s unknown whether these drugs, which have the same topoisomerase-targeted payload, could be given in sequence, and there are as yet no clear answers as to whether patients might do better with Dato-DXd or with a PIK3ca inhibitor.

“I would say that the elephant in the room is really another question, and that is, ‘Is Dato-DXd in this context delivering on the promise of an ADC?’ ” Dr. Chandarlapaty said.

“I think translational research is urgently needed if we’re ultimately to deliver on the promise of these agents in the clinic,” he concluded.

The TROPION-Breast01 study is sponsored AstraZeneca, which is collaborating with Daiichi-Sankyo on global development and commercialization of Dato-DXd. Dr. Bardia disclosed advisory board activities and institutional research funding from AstraZeneca and Daiichi-Sankyo and others. Dr. Chandarlapaty disclosed research funding from both companies, and advisory board activities for AstraZeneca and others.

The investigational anti-body drug conjugate (ADC) datopotamab deruxtecan (Dato-DXd) was associated with both improved progression-free survival and better safety than standard chemotherapy for patients with metastatic HER-2 negative (HR+/HER2–) breast cancer resistant to endocrine therapy, data from the phase 3 TROPION-Breast01 trial showed.

At a median follow-up of 10.8 months, the median progression-free survival (PFS) was 6.9 months for patients randomly assigned to receive Dato-DXd, compared with 4.9 months for the investigator’s choice of chemotherapy with either eribulin mesylate, vinorelbine, capecitabine, or gemcitabine. This difference translated into a 37% reduction in risk of disease progression with the ADC, reported Aditya Bardia, MD, MPH, director of the breast cancer research program at the Mass General Cancer Center in Boston.

Patients who received Dato-DXd had less than half the number of grade 3 or greater toxicities and fewer dose reductions or interruptions than patients who received chemotherapy, he noted in an oral abstract session at the 2023 European Society for Medical Oncology Congress.

“Overall, results support Dato-DXd as a potential new therapeutic option for patients with metastatic hormone receptor–positive breast cancer,” he said.
 

Different ADC, same target

Dr. Bardia noted that there is an unmet need for effective therapies for patients with metastatic HR+/HER2– breast cancer who experience disease progression after endocrine therapy and at least one line of systemic therapy.

Although chemotherapy is widely used in this population, it’s associated with low response rates, poor prognosis, and significant toxicities, including hematologic and neurologic adverse events (AEs).

Dato-DXd is composed of a monoclonal antibody targeting TROP2, a transmembrane glycoprotein overexpressed in cancer cells, linked to the topoisomerase 1 inhibitor deruxtecan as the toxic payload.

Dr. Bardia explained that Dato-DXd has four properties that distinguish it from other TROP2-directed ADCs: an optimized drug to antibody ratio of 4, a stable linker-payload, tumor-selective cleavable linker, both of which reduce off-target toxicities, and a bystander antitumor effect that can target TROP2-expressing cells in the tumor microenvironment.

In the phase I TROPION-PanTumor01 trial, Dato-DXd had promising anti-tumor activity and a manageable safety profile in patients with metastatic HR+/HER2– breast cancer, paving the way for the TROPION-Breast01 study reported here.
 

Efficacy results

In the Breast01 trial, 732 patients with inoperable or metastatic HR+/HER2– breast cancer previously treated with 1 or 2 lines of chemotherapy that had progressed on endocrine therapy were stratified by number of prior chemotherapy lines, geographic region, and prior CDK4/6 inhibitor status, and then randomized to either Dato-DXd 6 mg/kg intravenously on day 1 of each 3-week cycle (365 patients) or to investigator’s choice of chemotherapy (367 patients). According to the protocol, chemotherapy could be eribulin mesylate, vinorelbine, or gemcitabine delivered via IV on days 1 and 8 every 3 weeks, or oral capecitabine on days 1 through 14 of every 3-week cycle.

At the time of data cutoff, 93 patients assigned to the ADC and 39 assigned to chemotherapy were still on treatment.

As noted before, median PFS by blinded independent central review, one of two primary endpoints, was 6.9 months with Dato-DXd, compared with 4.9 months with chemotherapy, translating into a hazard ratio for progression of 0.63 (P < .0001)­­­.

The benefit was seen across nearly all subgroups except among patients who had not previously received a CDK4/6 inhibitor, and patients who had received a prior anthracycline but not a taxane.­

Objective response rates (ORR) were 36.4% with Dato-DXd (99.5% partial and .5% complete response), compared with 22.9% with chemotherapy (all partial responses; P values not reported).

Overall survival data, the other primary endpoint, were not mature at a median OS follow-up of 9.7 months, and will be reported at a later date.
 

­Safety results

“In terms of safety, the rate of grade 3 or higher treatment-related AEs in the Dato-DXd arm was less as compared to investigator choice of chemotherapy. This is a bit different from most of the studies; in general we see that the rate of adverse events is higher in the intervention arm as compared to the control arm,” Dr. Bardia commented.

Rates of dose reductions and dose interruptions due to treatment-related AEs were also lower with the ADC.

There were no patient deaths associated with Dato-DXd. One patient assigned to chemotherapy died from a complication associated with febrile neutropenia.

Most treatment-related AEs occurring in 15% of patients and AEs of special interest were of grade 1 and manageable.

The most common toxicities seen with the ADC were oral mucositis and dry eye. The most common side effects with chemotherapy were neutropenia and anemia, “the usual side effects you would expect with chemotherapy,” Dr. Bardia said, pointing out that the rate of grade 3 neutropenia was 31% with standard chemotherapy, compared with 1% with Dato-DXd.
 

Good, but we can do better

ESMO invited discussant Sarat Chandarlapaty, MD, PhD, a breast oncologist at Memorial Sloan Kettering Cancer Center in New York, commented that while the trial data showed superior efficacy and safety with Dato-DXd, compared with standard chemotherapy, it’s still unclear how it and other ADCs on the market and in the research pipeline may be used in therapy for this patient population.

“Would I rather prescribe Dato-DXd or more chemo after 1 to 2 lines of chemo in unselected HR-positive, HER2-negative breast cancer? The answer is Dato-DXd, but it leaves several unanswered questions for us,” he said.

“First, we have two ADCs approved in HR-positive breast cancer: another TROP2 ADC sacituzumab [govitecan] and a HER2 ADC trastuzumab deruxtecan. Would I rather give Dato over one of these? I don’t have an answer,” he added.

In addition, it’s unknown whether these drugs, which have the same topoisomerase-targeted payload, could be given in sequence, and there are as yet no clear answers as to whether patients might do better with Dato-DXd or with a PIK3ca inhibitor.

“I would say that the elephant in the room is really another question, and that is, ‘Is Dato-DXd in this context delivering on the promise of an ADC?’ ” Dr. Chandarlapaty said.

“I think translational research is urgently needed if we’re ultimately to deliver on the promise of these agents in the clinic,” he concluded.

The TROPION-Breast01 study is sponsored AstraZeneca, which is collaborating with Daiichi-Sankyo on global development and commercialization of Dato-DXd. Dr. Bardia disclosed advisory board activities and institutional research funding from AstraZeneca and Daiichi-Sankyo and others. Dr. Chandarlapaty disclosed research funding from both companies, and advisory board activities for AstraZeneca and others.

There is an urgent need to raise global awareness about the direct link between alcohol consumption and cancer risk.

That message was delivered by Isabelle Soerjomataram, PhD, with the International Agency for Research on Cancer (IARC), Lyon, France, at a session devoted to alcohol and cancer at the annual meeting of the European Society for Medical Oncology.

“Global awareness about the link between alcohol and cancer continues to be very low,” Dr. Soerjomataram told the audience. “Health professionals – oncologists, nurses, medical doctors, GPs – have an important role in increasing awareness and bringing this knowledge to people, which may lead to reduced consumption.”

Session chair Gilberto Morgan, MD, medical oncologist, Skåne University Hospital, Lund, Sweden, agreed.

Dr. Morgan noted that healthcare professionals tend to downplay their influence over patients’ drinking habits and often don’t address these behaviors.

But that needs to change.

“We have absolutely no problem asking patients if they take supplements or vitamins or if they’re eating [healthy],” Dr. Morgan said. “So, what is the difference? Why not recommend that they cut down their alcohol intake and leave it up to everybody’s personal choice to do it or not?”

In the session, Dr. Soerjomataram highlighted the global statistics on alcohol use. IARC data show, for instance, that nearly half (46%) of the world’s population consumes alcohol, with rates higher in men (54%) than women (38%).

How much are people drinking?

Globally, on average, the amount comes to about six liters of pure ethanol per year per drinker, or about one wine bottle per week. However, consumption patterns vary widely by country. In France, people consume about 12 liters per year or about two wine bottles per week.

Dr. Soerjomataram stressed the link between alcohol consumption and cancer.

According to IARC data, heavy drinking – defined as more than 60 g/day or about six daily drinks – accounts for 47% of the alcohol-attributable cancers. Risky drinking – between 20 and 60 g/day – accounts for 29%, she explained, while moderate drinking – less than 20 g/day or about two daily drinks – accounts for roughly 14% of cases of alcohol-attributable cancers.

Globally, alcohol intake accounted for 4% of all cancers diagnosed in 2020, according to a 2021 analysis by IARC. 

In the United Kingdom alone, “alcohol drinking caused nearly 17,000 cases of cancer in 2020,” Dr. Soerjomataram said, and breast cancer made up almost one in four of those new cases.

In addition to breast cancer, six other cancer types – oral cavity, pharyngeal, laryngeal, esophageal, colorectal, and liver cancer – can be attributed to alcohol consumption, and emerging evidence suggests stomach and pancreatic cancer may be as well.

The good news, said Dr. Soerjomataram, is that long-term trends show declines in alcohol drinking in many countries, including the high wine-producing countries of France and Italy, where large reductions in consumption have been noted since the peak of intake in the 1920s.

“If it’s possible in these countries, I can imagine it’s possible elsewhere,” said Dr. Soerjomataram. 

Dr. Soerjomataram and Dr. Morgan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There is an urgent need to raise global awareness about the direct link between alcohol consumption and cancer risk.

That message was delivered by Isabelle Soerjomataram, PhD, with the International Agency for Research on Cancer (IARC), Lyon, France, at a session devoted to alcohol and cancer at the annual meeting of the European Society for Medical Oncology.

“Global awareness about the link between alcohol and cancer continues to be very low,” Dr. Soerjomataram told the audience. “Health professionals – oncologists, nurses, medical doctors, GPs – have an important role in increasing awareness and bringing this knowledge to people, which may lead to reduced consumption.”

Session chair Gilberto Morgan, MD, medical oncologist, Skåne University Hospital, Lund, Sweden, agreed.

Dr. Morgan noted that healthcare professionals tend to downplay their influence over patients’ drinking habits and often don’t address these behaviors.

But that needs to change.

“We have absolutely no problem asking patients if they take supplements or vitamins or if they’re eating [healthy],” Dr. Morgan said. “So, what is the difference? Why not recommend that they cut down their alcohol intake and leave it up to everybody’s personal choice to do it or not?”

In the session, Dr. Soerjomataram highlighted the global statistics on alcohol use. IARC data show, for instance, that nearly half (46%) of the world’s population consumes alcohol, with rates higher in men (54%) than women (38%).

How much are people drinking?

Globally, on average, the amount comes to about six liters of pure ethanol per year per drinker, or about one wine bottle per week. However, consumption patterns vary widely by country. In France, people consume about 12 liters per year or about two wine bottles per week.

Dr. Soerjomataram stressed the link between alcohol consumption and cancer.

According to IARC data, heavy drinking – defined as more than 60 g/day or about six daily drinks – accounts for 47% of the alcohol-attributable cancers. Risky drinking – between 20 and 60 g/day – accounts for 29%, she explained, while moderate drinking – less than 20 g/day or about two daily drinks – accounts for roughly 14% of cases of alcohol-attributable cancers.

Globally, alcohol intake accounted for 4% of all cancers diagnosed in 2020, according to a 2021 analysis by IARC. 

In the United Kingdom alone, “alcohol drinking caused nearly 17,000 cases of cancer in 2020,” Dr. Soerjomataram said, and breast cancer made up almost one in four of those new cases.

In addition to breast cancer, six other cancer types – oral cavity, pharyngeal, laryngeal, esophageal, colorectal, and liver cancer – can be attributed to alcohol consumption, and emerging evidence suggests stomach and pancreatic cancer may be as well.

The good news, said Dr. Soerjomataram, is that long-term trends show declines in alcohol drinking in many countries, including the high wine-producing countries of France and Italy, where large reductions in consumption have been noted since the peak of intake in the 1920s.

“If it’s possible in these countries, I can imagine it’s possible elsewhere,” said Dr. Soerjomataram. 

Dr. Soerjomataram and Dr. Morgan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

There is an urgent need to raise global awareness about the direct link between alcohol consumption and cancer risk.

That message was delivered by Isabelle Soerjomataram, PhD, with the International Agency for Research on Cancer (IARC), Lyon, France, at a session devoted to alcohol and cancer at the annual meeting of the European Society for Medical Oncology.

“Global awareness about the link between alcohol and cancer continues to be very low,” Dr. Soerjomataram told the audience. “Health professionals – oncologists, nurses, medical doctors, GPs – have an important role in increasing awareness and bringing this knowledge to people, which may lead to reduced consumption.”

Session chair Gilberto Morgan, MD, medical oncologist, Skåne University Hospital, Lund, Sweden, agreed.

Dr. Morgan noted that healthcare professionals tend to downplay their influence over patients’ drinking habits and often don’t address these behaviors.

But that needs to change.

“We have absolutely no problem asking patients if they take supplements or vitamins or if they’re eating [healthy],” Dr. Morgan said. “So, what is the difference? Why not recommend that they cut down their alcohol intake and leave it up to everybody’s personal choice to do it or not?”

In the session, Dr. Soerjomataram highlighted the global statistics on alcohol use. IARC data show, for instance, that nearly half (46%) of the world’s population consumes alcohol, with rates higher in men (54%) than women (38%).

How much are people drinking?

Globally, on average, the amount comes to about six liters of pure ethanol per year per drinker, or about one wine bottle per week. However, consumption patterns vary widely by country. In France, people consume about 12 liters per year or about two wine bottles per week.

Dr. Soerjomataram stressed the link between alcohol consumption and cancer.

According to IARC data, heavy drinking – defined as more than 60 g/day or about six daily drinks – accounts for 47% of the alcohol-attributable cancers. Risky drinking – between 20 and 60 g/day – accounts for 29%, she explained, while moderate drinking – less than 20 g/day or about two daily drinks – accounts for roughly 14% of cases of alcohol-attributable cancers.

Globally, alcohol intake accounted for 4% of all cancers diagnosed in 2020, according to a 2021 analysis by IARC. 

In the United Kingdom alone, “alcohol drinking caused nearly 17,000 cases of cancer in 2020,” Dr. Soerjomataram said, and breast cancer made up almost one in four of those new cases.

In addition to breast cancer, six other cancer types – oral cavity, pharyngeal, laryngeal, esophageal, colorectal, and liver cancer – can be attributed to alcohol consumption, and emerging evidence suggests stomach and pancreatic cancer may be as well.

The good news, said Dr. Soerjomataram, is that long-term trends show declines in alcohol drinking in many countries, including the high wine-producing countries of France and Italy, where large reductions in consumption have been noted since the peak of intake in the 1920s.

“If it’s possible in these countries, I can imagine it’s possible elsewhere,” said Dr. Soerjomataram. 

Dr. Soerjomataram and Dr. Morgan report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Further evidence for the benefit of adding immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early high-risk estrogen receptor–positive, HER2-negative (HR+/HER2–) breast cancer comes from results of two randomized trials presented at the annual meeting of the European Society for Medical Oncology.

In the KEYNOTE-756 trial, adding pembrolizumab (Keytruda) to neoadjuvant chemotherapy resulted in an 8.5% increase in pathologic complete response (pCR) rates, compared with chemotherapy alone, regardless of the patients’ programmed death ligand-1 (PD-L1) status, reported Fatima Cardoso, MD, director of the breast unit at the Champalimaud Clinical Center in Lisbon.

In the Checkmate 7FL trial, a study bedeviled by unexpected circumstances, the addition of nivolumab (Opdivo) to neoadjuvant chemotherapy resulted in a 10.5% absolute increase in pCR rates, compared with chemotherapy alone, reported Sherene Loi, MBBS, PhD, from the Peter MacCallum Cancer Centre in Melbourne.

A new paradigm?

Taken together, the trials suggest that neoadjuvant immunotherapy has the potential to be “a new paradigm,” said ESMO invited discussant Steven RD Johnston, MD, PhD, professor of breast cancer medicine at the Royal Marsden Hospital and Institute of Cancer Research in London.

“Is the management of ER-positive breast cancer going to change with immunotherapy? Can we improve pCR rates? Yes, we can. We’ve seen a significant improvement in two separate studies, albeit the rates are only at 24%, and at this point, it’s unclear if this will translate into a better event-free survival [EFS] because we have to wait and follow the data,” he said.

The data from the two studies suggest that the patients who are likely to benefit most would be those with higher-grade tumors, luminal B subtype tumors, and, possibly, those whose tumors express higher levels of PD-L1, although the definition of PD-L1 positive depends on the assay used, he said

“I think we have to make better efforts to evaluate whether genomic or immune signatures can further define those who have most to gain, and I would urge investigators in both studies to do more digging into understanding this, because you might really enrich the patients who have the most to gain from the is approach,” Dr. Johnston said.

Checkmate 7FL details

In this prospective, randomized multicenter trial patients received four cycles of neoadjuvant paclitaxel followed by four cycles of doxorubicin and cyclophosphamide (AC) and surgery with adjuvant endocrine therapy. In arm A, 257 patients received neoadjuvant and adjuvant nivolumab. In arm B 253, patients received a nivolumab placebo in both the neoadjuvant and adjuvant settings.

Eligible patients had newly diagnosed ER+/HER2– breast cancer centrally confirmed. Patients with T1c or T2 tumors who were clinically node positive on histology and those with T3 or T4 tumors of any nodal status were eligible. Patients were required to have grade 3 histology as determined by the local pathologist, or grade 2 with low ER expression.

Patients were stratified by PD-L1 status, tumor grade, axillary nodal status and frequency of AC delivery (every 2 or 3 weeks) and were then randomized into one of the two treatment arms.

Destiny takes a hand

The protocol was changed following the approval in October 2021 of adjuvant abemaciclib in patients with high-risk ER+/HER2– disease.

“This was expected to result in a high rate of withdrawals due to safety concerns when combining a CDK4/6 inhibitor with an anti-PD-1, and this put the co-primary endpoint of EFS at risk,” Dr. Loi explained.

Therefore, the investigators amended the trial protocol to establish pCR as the sole primary endpoint and ceased accrual after 521 patients were randomized.

In addition, the primary efficacy population was modified to include 510 patients across 221 sites in 31 countries after Russian sites with a total of 11 patients closed due to Russia’s war on Ukraine.

And another hurdle, trial recruitment occurred from November 2019 through April 2022, during the COVID-19 pandemic.

Checkmate 7FL results

The pCR rate in the modified intention-to-treat (ITT) population was 24.5% for patients who received nivolumab, compared with 13.8% for patients who did not, translating in an odds ratio for benefit with the ICI of 2.05 (P = .0021),

In patients with PD-L1 expression in at least 1% of cells, a secondary endpoint, the respective pCR rates were 44.3% and 20.2%, with OR of 3.11, and a confidence interval indicating statistical significance.

Residual cancer burden (RCB) rates of 0 or 1 were also higher in the nivolumab-containing arm in both the modified ITT population (30.7% vs. 21.3%), and in the PD-L1–enriched population (54.5% vs. 26.2%).

In the safety population, which included 517 patients who received at least one dose of nivolumab or placebo, rates of overall adverse events and treatment-related adverse events were similar between the two arms, with the exception of two deaths from drug toxicity in Arm A (from pneumonitis in a patient 61 days after the last neoadjuvant cycles and hepatitis in a patient 51 days after) vs. no drug toxicity deaths reported in Arm B.

Safety of the nivolumab and neoadjuvant chemotherapy combinations was consistent with known safety profiles, with no new safety signals seen, Dr. Loi said.

KEYNOTE-756 details

The KEYNOTE-756 investigators had an easier time of it than Dr. Loi and colleagues. In fact, the trial “is the first fully accrued phase 3 immunotherapy study in high-risk, early-stage ER-positive, HER2-negative breast cancer, and it met one of its primary endpoints, pCR,” Dr. Cardoso said.

She noted that in the adaptive I-SPY2 trial, the addition of pembrolizumab to neoadjuvant chemotherapy resulted in a nearly threefold improvement in estimated pCR rates in patients with ER+/HER2– tumors, indicating that the role of immunotherapy in this population warranted further exploration.

In the placebo-controlled KEYNOTE-756 trial, treatment-naive patients with locally confirmed invasive ductal breast carcinoma with stage T1c or T2 tumors 2 cm or larger with nodal status CN1 or 2, or T3 and T4 tumors with nodal status CN0-2 were enrolled.

In most centers (Eastern Europe and China being the exceptions) patients were stratified by PD-L1 status, nodal status, anthracycline regimen chosen (AC or epirubicin-cyclophosphamide [EC]) and by degree of ER-positivity. Patients, 1,278 in total, were then randomly assigned to pembrolizumab for four cycles plus paclitaxel for 12 weeks, followed by AC or EC for four cycles plus pembrolizumab, or to the same regimen without pembrolizumab.

Following surgery, patients went on to endocrine therapy for up to 10 years, with or without 6 months of additional pembrolizumab every 6 months.

KEYNOTE-756 results

For the ITT analysis, 635 patients assigned to pembrolizumab and 643 assigned to placebo were evaluable.

At the first interim assessment, conducted at a median follow-up of 33.2 months, with the longest follow-up out to 51.8 months, the co-primary endpoint of an improvement in pCR with immunotherapy was met. The pCR rate with pembrolizumab was 24.3%, compared with 15.6% with placebo, an absolute difference of 8.5% (P = .00005).

Data for the other co-primary endpoint, EFS, were not mature at the time of data cutoff, and will be reported at a future date, Dr. Cardoso said.

An analysis of pCR rates in subgroups showed that pembrolizumab benefited most patients, with the exception of those 65 years and older, patients with Eastern Cooperative Oncology Group performance status of 1 (vs. 0), patients who received their anthracycline regimen every 2 weeks rather than every 3, and node-negative patients.

The benefit was particular pronounced among patients with less than 10% ER positivity, she pointed out.

Adverse events in the neoadjuvant phase were primarily related to chemotherapy, with no major differences between the arms, although grade 3 or greater events were slightly more frequent with pembrolizumab (52.5% vs. 46.4%), and two patients in the pembrolizumab arm died (one death was from acute myocardial infarction considered related to the long QT syndrome; cause of the other patient’s death was not specified).

Adverse events leading to discontinuation were also more common with pembrolizumab (19.1% vs. 10.1%, respectively).

Immune-mediated adverse events of any grade were also higher in the immunotherapy arm, occurring in 32.8% of patients vs. 7% of patients in the placebo arm.

There were no deaths from immune-related adverse events.

Eye on safety

In his discussion, Dr. Johnston emphasized that “it’s important in a curative population that we don’t harm patients in a setting where we have a variety of other therapies available.”

Recalling the deaths of patients in the immunotherapy arm of each trial, he commented that “deaths in early breast cancer in a treatment setting are always a disaster, and we have to make sure that we manage these adverse events as we can best, and we know how to do that now.”

Checkmate 7FL was supported by Bristol Myers Squibb. Dr. Loi reported financial and nonfinancial interests with BMS and with other companies. KEYNOTE-756 was supported by Merck Sharp & Dohme. Dr. Cardoso disclosed consulting and institutional research support from Merck and others. Dr. Johnston reported consulting or advisory roles, honoraria, and research funding from several companies, not including either BMS or Merck.

Further evidence for the benefit of adding immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early high-risk estrogen receptor–positive, HER2-negative (HR+/HER2–) breast cancer comes from results of two randomized trials presented at the annual meeting of the European Society for Medical Oncology.

In the KEYNOTE-756 trial, adding pembrolizumab (Keytruda) to neoadjuvant chemotherapy resulted in an 8.5% increase in pathologic complete response (pCR) rates, compared with chemotherapy alone, regardless of the patients’ programmed death ligand-1 (PD-L1) status, reported Fatima Cardoso, MD, director of the breast unit at the Champalimaud Clinical Center in Lisbon.

In the Checkmate 7FL trial, a study bedeviled by unexpected circumstances, the addition of nivolumab (Opdivo) to neoadjuvant chemotherapy resulted in a 10.5% absolute increase in pCR rates, compared with chemotherapy alone, reported Sherene Loi, MBBS, PhD, from the Peter MacCallum Cancer Centre in Melbourne.

A new paradigm?

Taken together, the trials suggest that neoadjuvant immunotherapy has the potential to be “a new paradigm,” said ESMO invited discussant Steven RD Johnston, MD, PhD, professor of breast cancer medicine at the Royal Marsden Hospital and Institute of Cancer Research in London.

“Is the management of ER-positive breast cancer going to change with immunotherapy? Can we improve pCR rates? Yes, we can. We’ve seen a significant improvement in two separate studies, albeit the rates are only at 24%, and at this point, it’s unclear if this will translate into a better event-free survival [EFS] because we have to wait and follow the data,” he said.

The data from the two studies suggest that the patients who are likely to benefit most would be those with higher-grade tumors, luminal B subtype tumors, and, possibly, those whose tumors express higher levels of PD-L1, although the definition of PD-L1 positive depends on the assay used, he said

“I think we have to make better efforts to evaluate whether genomic or immune signatures can further define those who have most to gain, and I would urge investigators in both studies to do more digging into understanding this, because you might really enrich the patients who have the most to gain from the is approach,” Dr. Johnston said.

Checkmate 7FL details

In this prospective, randomized multicenter trial patients received four cycles of neoadjuvant paclitaxel followed by four cycles of doxorubicin and cyclophosphamide (AC) and surgery with adjuvant endocrine therapy. In arm A, 257 patients received neoadjuvant and adjuvant nivolumab. In arm B 253, patients received a nivolumab placebo in both the neoadjuvant and adjuvant settings.

Eligible patients had newly diagnosed ER+/HER2– breast cancer centrally confirmed. Patients with T1c or T2 tumors who were clinically node positive on histology and those with T3 or T4 tumors of any nodal status were eligible. Patients were required to have grade 3 histology as determined by the local pathologist, or grade 2 with low ER expression.

Patients were stratified by PD-L1 status, tumor grade, axillary nodal status and frequency of AC delivery (every 2 or 3 weeks) and were then randomized into one of the two treatment arms.

Destiny takes a hand

The protocol was changed following the approval in October 2021 of adjuvant abemaciclib in patients with high-risk ER+/HER2– disease.

“This was expected to result in a high rate of withdrawals due to safety concerns when combining a CDK4/6 inhibitor with an anti-PD-1, and this put the co-primary endpoint of EFS at risk,” Dr. Loi explained.

Therefore, the investigators amended the trial protocol to establish pCR as the sole primary endpoint and ceased accrual after 521 patients were randomized.

In addition, the primary efficacy population was modified to include 510 patients across 221 sites in 31 countries after Russian sites with a total of 11 patients closed due to Russia’s war on Ukraine.

And another hurdle, trial recruitment occurred from November 2019 through April 2022, during the COVID-19 pandemic.

Checkmate 7FL results

The pCR rate in the modified intention-to-treat (ITT) population was 24.5% for patients who received nivolumab, compared with 13.8% for patients who did not, translating in an odds ratio for benefit with the ICI of 2.05 (P = .0021),

In patients with PD-L1 expression in at least 1% of cells, a secondary endpoint, the respective pCR rates were 44.3% and 20.2%, with OR of 3.11, and a confidence interval indicating statistical significance.

Residual cancer burden (RCB) rates of 0 or 1 were also higher in the nivolumab-containing arm in both the modified ITT population (30.7% vs. 21.3%), and in the PD-L1–enriched population (54.5% vs. 26.2%).

In the safety population, which included 517 patients who received at least one dose of nivolumab or placebo, rates of overall adverse events and treatment-related adverse events were similar between the two arms, with the exception of two deaths from drug toxicity in Arm A (from pneumonitis in a patient 61 days after the last neoadjuvant cycles and hepatitis in a patient 51 days after) vs. no drug toxicity deaths reported in Arm B.

Safety of the nivolumab and neoadjuvant chemotherapy combinations was consistent with known safety profiles, with no new safety signals seen, Dr. Loi said.

KEYNOTE-756 details

The KEYNOTE-756 investigators had an easier time of it than Dr. Loi and colleagues. In fact, the trial “is the first fully accrued phase 3 immunotherapy study in high-risk, early-stage ER-positive, HER2-negative breast cancer, and it met one of its primary endpoints, pCR,” Dr. Cardoso said.

She noted that in the adaptive I-SPY2 trial, the addition of pembrolizumab to neoadjuvant chemotherapy resulted in a nearly threefold improvement in estimated pCR rates in patients with ER+/HER2– tumors, indicating that the role of immunotherapy in this population warranted further exploration.

In the placebo-controlled KEYNOTE-756 trial, treatment-naive patients with locally confirmed invasive ductal breast carcinoma with stage T1c or T2 tumors 2 cm or larger with nodal status CN1 or 2, or T3 and T4 tumors with nodal status CN0-2 were enrolled.

In most centers (Eastern Europe and China being the exceptions) patients were stratified by PD-L1 status, nodal status, anthracycline regimen chosen (AC or epirubicin-cyclophosphamide [EC]) and by degree of ER-positivity. Patients, 1,278 in total, were then randomly assigned to pembrolizumab for four cycles plus paclitaxel for 12 weeks, followed by AC or EC for four cycles plus pembrolizumab, or to the same regimen without pembrolizumab.

Following surgery, patients went on to endocrine therapy for up to 10 years, with or without 6 months of additional pembrolizumab every 6 months.

KEYNOTE-756 results

For the ITT analysis, 635 patients assigned to pembrolizumab and 643 assigned to placebo were evaluable.

At the first interim assessment, conducted at a median follow-up of 33.2 months, with the longest follow-up out to 51.8 months, the co-primary endpoint of an improvement in pCR with immunotherapy was met. The pCR rate with pembrolizumab was 24.3%, compared with 15.6% with placebo, an absolute difference of 8.5% (P = .00005).

Data for the other co-primary endpoint, EFS, were not mature at the time of data cutoff, and will be reported at a future date, Dr. Cardoso said.

An analysis of pCR rates in subgroups showed that pembrolizumab benefited most patients, with the exception of those 65 years and older, patients with Eastern Cooperative Oncology Group performance status of 1 (vs. 0), patients who received their anthracycline regimen every 2 weeks rather than every 3, and node-negative patients.

The benefit was particular pronounced among patients with less than 10% ER positivity, she pointed out.

Adverse events in the neoadjuvant phase were primarily related to chemotherapy, with no major differences between the arms, although grade 3 or greater events were slightly more frequent with pembrolizumab (52.5% vs. 46.4%), and two patients in the pembrolizumab arm died (one death was from acute myocardial infarction considered related to the long QT syndrome; cause of the other patient’s death was not specified).

Adverse events leading to discontinuation were also more common with pembrolizumab (19.1% vs. 10.1%, respectively).

Immune-mediated adverse events of any grade were also higher in the immunotherapy arm, occurring in 32.8% of patients vs. 7% of patients in the placebo arm.

There were no deaths from immune-related adverse events.

Eye on safety

In his discussion, Dr. Johnston emphasized that “it’s important in a curative population that we don’t harm patients in a setting where we have a variety of other therapies available.”

Recalling the deaths of patients in the immunotherapy arm of each trial, he commented that “deaths in early breast cancer in a treatment setting are always a disaster, and we have to make sure that we manage these adverse events as we can best, and we know how to do that now.”

Checkmate 7FL was supported by Bristol Myers Squibb. Dr. Loi reported financial and nonfinancial interests with BMS and with other companies. KEYNOTE-756 was supported by Merck Sharp & Dohme. Dr. Cardoso disclosed consulting and institutional research support from Merck and others. Dr. Johnston reported consulting or advisory roles, honoraria, and research funding from several companies, not including either BMS or Merck.

Further evidence for the benefit of adding immune checkpoint inhibitors to neoadjuvant chemotherapy in patients with early high-risk estrogen receptor–positive, HER2-negative (HR+/HER2–) breast cancer comes from results of two randomized trials presented at the annual meeting of the European Society for Medical Oncology.

In the KEYNOTE-756 trial, adding pembrolizumab (Keytruda) to neoadjuvant chemotherapy resulted in an 8.5% increase in pathologic complete response (pCR) rates, compared with chemotherapy alone, regardless of the patients’ programmed death ligand-1 (PD-L1) status, reported Fatima Cardoso, MD, director of the breast unit at the Champalimaud Clinical Center in Lisbon.

In the Checkmate 7FL trial, a study bedeviled by unexpected circumstances, the addition of nivolumab (Opdivo) to neoadjuvant chemotherapy resulted in a 10.5% absolute increase in pCR rates, compared with chemotherapy alone, reported Sherene Loi, MBBS, PhD, from the Peter MacCallum Cancer Centre in Melbourne.

A new paradigm?

Taken together, the trials suggest that neoadjuvant immunotherapy has the potential to be “a new paradigm,” said ESMO invited discussant Steven RD Johnston, MD, PhD, professor of breast cancer medicine at the Royal Marsden Hospital and Institute of Cancer Research in London.

“Is the management of ER-positive breast cancer going to change with immunotherapy? Can we improve pCR rates? Yes, we can. We’ve seen a significant improvement in two separate studies, albeit the rates are only at 24%, and at this point, it’s unclear if this will translate into a better event-free survival [EFS] because we have to wait and follow the data,” he said.

The data from the two studies suggest that the patients who are likely to benefit most would be those with higher-grade tumors, luminal B subtype tumors, and, possibly, those whose tumors express higher levels of PD-L1, although the definition of PD-L1 positive depends on the assay used, he said

“I think we have to make better efforts to evaluate whether genomic or immune signatures can further define those who have most to gain, and I would urge investigators in both studies to do more digging into understanding this, because you might really enrich the patients who have the most to gain from the is approach,” Dr. Johnston said.

Checkmate 7FL details

In this prospective, randomized multicenter trial patients received four cycles of neoadjuvant paclitaxel followed by four cycles of doxorubicin and cyclophosphamide (AC) and surgery with adjuvant endocrine therapy. In arm A, 257 patients received neoadjuvant and adjuvant nivolumab. In arm B 253, patients received a nivolumab placebo in both the neoadjuvant and adjuvant settings.

Eligible patients had newly diagnosed ER+/HER2– breast cancer centrally confirmed. Patients with T1c or T2 tumors who were clinically node positive on histology and those with T3 or T4 tumors of any nodal status were eligible. Patients were required to have grade 3 histology as determined by the local pathologist, or grade 2 with low ER expression.

Patients were stratified by PD-L1 status, tumor grade, axillary nodal status and frequency of AC delivery (every 2 or 3 weeks) and were then randomized into one of the two treatment arms.

Destiny takes a hand

The protocol was changed following the approval in October 2021 of adjuvant abemaciclib in patients with high-risk ER+/HER2– disease.

“This was expected to result in a high rate of withdrawals due to safety concerns when combining a CDK4/6 inhibitor with an anti-PD-1, and this put the co-primary endpoint of EFS at risk,” Dr. Loi explained.

Therefore, the investigators amended the trial protocol to establish pCR as the sole primary endpoint and ceased accrual after 521 patients were randomized.

In addition, the primary efficacy population was modified to include 510 patients across 221 sites in 31 countries after Russian sites with a total of 11 patients closed due to Russia’s war on Ukraine.

And another hurdle, trial recruitment occurred from November 2019 through April 2022, during the COVID-19 pandemic.

Checkmate 7FL results

The pCR rate in the modified intention-to-treat (ITT) population was 24.5% for patients who received nivolumab, compared with 13.8% for patients who did not, translating in an odds ratio for benefit with the ICI of 2.05 (P = .0021),

In patients with PD-L1 expression in at least 1% of cells, a secondary endpoint, the respective pCR rates were 44.3% and 20.2%, with OR of 3.11, and a confidence interval indicating statistical significance.

Residual cancer burden (RCB) rates of 0 or 1 were also higher in the nivolumab-containing arm in both the modified ITT population (30.7% vs. 21.3%), and in the PD-L1–enriched population (54.5% vs. 26.2%).

In the safety population, which included 517 patients who received at least one dose of nivolumab or placebo, rates of overall adverse events and treatment-related adverse events were similar between the two arms, with the exception of two deaths from drug toxicity in Arm A (from pneumonitis in a patient 61 days after the last neoadjuvant cycles and hepatitis in a patient 51 days after) vs. no drug toxicity deaths reported in Arm B.

Safety of the nivolumab and neoadjuvant chemotherapy combinations was consistent with known safety profiles, with no new safety signals seen, Dr. Loi said.

KEYNOTE-756 details

The KEYNOTE-756 investigators had an easier time of it than Dr. Loi and colleagues. In fact, the trial “is the first fully accrued phase 3 immunotherapy study in high-risk, early-stage ER-positive, HER2-negative breast cancer, and it met one of its primary endpoints, pCR,” Dr. Cardoso said.

She noted that in the adaptive I-SPY2 trial, the addition of pembrolizumab to neoadjuvant chemotherapy resulted in a nearly threefold improvement in estimated pCR rates in patients with ER+/HER2– tumors, indicating that the role of immunotherapy in this population warranted further exploration.

In the placebo-controlled KEYNOTE-756 trial, treatment-naive patients with locally confirmed invasive ductal breast carcinoma with stage T1c or T2 tumors 2 cm or larger with nodal status CN1 or 2, or T3 and T4 tumors with nodal status CN0-2 were enrolled.

In most centers (Eastern Europe and China being the exceptions) patients were stratified by PD-L1 status, nodal status, anthracycline regimen chosen (AC or epirubicin-cyclophosphamide [EC]) and by degree of ER-positivity. Patients, 1,278 in total, were then randomly assigned to pembrolizumab for four cycles plus paclitaxel for 12 weeks, followed by AC or EC for four cycles plus pembrolizumab, or to the same regimen without pembrolizumab.

Following surgery, patients went on to endocrine therapy for up to 10 years, with or without 6 months of additional pembrolizumab every 6 months.

KEYNOTE-756 results

For the ITT analysis, 635 patients assigned to pembrolizumab and 643 assigned to placebo were evaluable.

At the first interim assessment, conducted at a median follow-up of 33.2 months, with the longest follow-up out to 51.8 months, the co-primary endpoint of an improvement in pCR with immunotherapy was met. The pCR rate with pembrolizumab was 24.3%, compared with 15.6% with placebo, an absolute difference of 8.5% (P = .00005).

Data for the other co-primary endpoint, EFS, were not mature at the time of data cutoff, and will be reported at a future date, Dr. Cardoso said.

An analysis of pCR rates in subgroups showed that pembrolizumab benefited most patients, with the exception of those 65 years and older, patients with Eastern Cooperative Oncology Group performance status of 1 (vs. 0), patients who received their anthracycline regimen every 2 weeks rather than every 3, and node-negative patients.

The benefit was particular pronounced among patients with less than 10% ER positivity, she pointed out.

Adverse events in the neoadjuvant phase were primarily related to chemotherapy, with no major differences between the arms, although grade 3 or greater events were slightly more frequent with pembrolizumab (52.5% vs. 46.4%), and two patients in the pembrolizumab arm died (one death was from acute myocardial infarction considered related to the long QT syndrome; cause of the other patient’s death was not specified).

Adverse events leading to discontinuation were also more common with pembrolizumab (19.1% vs. 10.1%, respectively).

Immune-mediated adverse events of any grade were also higher in the immunotherapy arm, occurring in 32.8% of patients vs. 7% of patients in the placebo arm.

There were no deaths from immune-related adverse events.

Eye on safety

In his discussion, Dr. Johnston emphasized that “it’s important in a curative population that we don’t harm patients in a setting where we have a variety of other therapies available.”

Recalling the deaths of patients in the immunotherapy arm of each trial, he commented that “deaths in early breast cancer in a treatment setting are always a disaster, and we have to make sure that we manage these adverse events as we can best, and we know how to do that now.”

Checkmate 7FL was supported by Bristol Myers Squibb. Dr. Loi reported financial and nonfinancial interests with BMS and with other companies. KEYNOTE-756 was supported by Merck Sharp & Dohme. Dr. Cardoso disclosed consulting and institutional research support from Merck and others. Dr. Johnston reported consulting or advisory roles, honoraria, and research funding from several companies, not including either BMS or Merck.

Despite the proven benefit of adding an immune checkpoint inhibitor (ICI) to preoperative chemotherapy for patients with triple-negative breast cancer (TNBC), the NeoTRIP Michelangelo trial stumbled at the finish line, showing that adding atezolizumab (Tecentriq) to nab-paclitaxel and carboplatin followed by surgery and adjuvant anthracycline-based chemotherapy did not improve 5-year event-free survival (EFS), compared with the same regimen without atezolizumab.

Although the trial did not produce the desired result, it still provided important impetus for researchers to do better, said lead investigator Luca Gianni, MD, chair of the international breast cancer research committee at Fondazione Michelangelo in Milan.

“I strongly believe that the results of NeoTRIP, rather than being viewed as negative, should bring forth the search for dependable and widely applicable predictors of ICIs’ benefit in women with operable triple negative breast cancer,” he said in an oral abstract session at the annual meeting of the European Society for Medical Oncology.

Other neoadjuvant trials with different agents have shown benefit from the addition of an ICI to chemotherapy for patients with TNBC, Dr. Gianni noted, with pembrolizumab (Keytruda) in Keynote-522, durvalumab (Imfinzi) in GeparNuevo, and with atezolizumab in IMpassion031.

NeoTRIP results

Dr. Gianni and colleagues had previously reported that adding atezolizumab to neoadjuvant carboplatin/nab-paclitaxel did not significantly improve pathologic complete response rates (pCR) in the randomized trial, although other trials of neoadjuvant ICIs in this population had shown a pCR benefit.

“Our analysis of NeoTRIP supports that pCR may not be an appropriate surrogate endpoint for the role of ICIs in early TNBC,” they wrote in that analysis.

At ESMO 2023, the investigators presented 5-year event-free survival rates, the primary study endpoint, and results of an exploratory analysis of predictive biomarkers.

In the phase 3 trial, patients with HER2-negative, estrogen receptor–negative, and progesterone receptor–negative early high-risk or locally advanced unilateral breast cancer were randomly assigned to receive eight cycles of carboplatin plus nab-paclitaxel with or without atezolizumab, followed by surgery and four cycles of an anthracycline-based chemotherapy regimen of the investigators choice.

A total of 280 patients were included in the intention-to-treat (ITT) population, including 138 assigned to receive atezolizumab and 142 who received chemotherapy alone.

Of these groups. 119 and 120, respectively, went on to surgery and were eligible for adjuvant chemotherapy. In all, 79 patients (66%) in the atezolizumab arm and 90 (75%) in the no-atezolizumab arm completed the four planned cycles of postoperative chemotherapy.

At a median follow-up of 54 months, the EFS rate with atezolizumab was 70.6%, compared with 74.9% without atezolizumab, translating into a nonsignificant hazard ratio of 1.076­­ for disease progression while on primary therapy or disease recurrence after surgery, or death from any cause, including unknown causes.

Pathologic complete responses key

In multivariate analysis, significant predictors for better EFS included achievement of a pCR; disease stage (early high risk vs. locally advanced); programmed death ligand-1 (PD-L1) levels above 1% as assessed by the SP142 assay; and higher levels of stromal tumor-infiltrating lymphocytes, but these factors were not predictive of atezolizumab benefit, Dr. Gianni said.

Among all patients who had a pCR, regardless of regimen, the 5-year EFS rate was 90.3%, compared with 55.7% for those who did not receive a pCR, translating into a hazard ratio of 0.19 for pathologic complete responses (P < .0001).

Looking at treatment-related adverse events occurring following surgery – that is, after atezolizumab therapy had stopped – they did not detect any new safety signals. The most common grade 3 or greater toxicity in each arm was neutropenia, followed by leukopenia, and in the atezolizumab arm there was one case of a grade 3 myocarditis that occurred 2 weeks after surgery and before the patient started on an anthracycline.

The authors also conducted a mass cytometry analysis of potential predictors of response to checkpoint inhibitors in TNBC, and reported the results in Nature.

“Basically, baseline density of several activated immune cells predicted for higher probability of pCR with atezolizumab but not with chemotherapy without atezolizumab,” Dr. Gianni said.

Specifically, they saw that high density of CD8-positive, TCF1-positive and Ki-67-positive markers were associated with increased pCR and EFS rates with the addition of atezolizumab.

Why no benefit to the ICI?

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University in Atlanta said that at least two possible explanations floated for the lack of either a pCR or EFS benefit in NeoTRIP don’t hold water.

For example, the theory that a difference in efficacy between PD-1 and PD-L1 inhibitors might explain the lack of benefit in NeoTRIP is undermined by IMpassion031, which showed pCR and EFS benefits with atezolizumab.

In addition, although NeoTRIP did not include an anthracycline in the neoadjuvant regimen, neither did the NeoPACT trial, in which patients received six cycles of neoadjuvant taxane, carboplatin, and pembrolizumab, and had a 58% pCR rate, with a high 2-year EFS rate among patients who had a pCR.

“As we know, triple-negative breast cancer is a heterogeneous disease. Could it be by chance that there are differences in tumor biology reflected across the various neoadjuvant trials, including molecular subtypes? Also in NeoTRIP, previously reported we’ve seen that there were a higher rate of TILs in the chemo-alone arm; high TILs can be associated with chemosensitivity, and maybe this influenced the results,” he said.

Predictive markers to immunotherapy in TNBC are still needed, he said, because neither PD-L1 expression, tumor mutational burden, or TILs have proven to be reliable biomarkers for this subtype.

The NeoTRIP Michelangelo trial was supported by Hoffman-La Roche and Celgene. Dr. Gianni disclosed financial interests with Roche and others including advisory board activity, consulting, and personal fees. Dr. Kalinsky reported advisory/consulting activities for various companies, including Genentech/Roche.

Despite the proven benefit of adding an immune checkpoint inhibitor (ICI) to preoperative chemotherapy for patients with triple-negative breast cancer (TNBC), the NeoTRIP Michelangelo trial stumbled at the finish line, showing that adding atezolizumab (Tecentriq) to nab-paclitaxel and carboplatin followed by surgery and adjuvant anthracycline-based chemotherapy did not improve 5-year event-free survival (EFS), compared with the same regimen without atezolizumab.

Although the trial did not produce the desired result, it still provided important impetus for researchers to do better, said lead investigator Luca Gianni, MD, chair of the international breast cancer research committee at Fondazione Michelangelo in Milan.

“I strongly believe that the results of NeoTRIP, rather than being viewed as negative, should bring forth the search for dependable and widely applicable predictors of ICIs’ benefit in women with operable triple negative breast cancer,” he said in an oral abstract session at the annual meeting of the European Society for Medical Oncology.

Other neoadjuvant trials with different agents have shown benefit from the addition of an ICI to chemotherapy for patients with TNBC, Dr. Gianni noted, with pembrolizumab (Keytruda) in Keynote-522, durvalumab (Imfinzi) in GeparNuevo, and with atezolizumab in IMpassion031.

NeoTRIP results

Dr. Gianni and colleagues had previously reported that adding atezolizumab to neoadjuvant carboplatin/nab-paclitaxel did not significantly improve pathologic complete response rates (pCR) in the randomized trial, although other trials of neoadjuvant ICIs in this population had shown a pCR benefit.

“Our analysis of NeoTRIP supports that pCR may not be an appropriate surrogate endpoint for the role of ICIs in early TNBC,” they wrote in that analysis.

At ESMO 2023, the investigators presented 5-year event-free survival rates, the primary study endpoint, and results of an exploratory analysis of predictive biomarkers.

In the phase 3 trial, patients with HER2-negative, estrogen receptor–negative, and progesterone receptor–negative early high-risk or locally advanced unilateral breast cancer were randomly assigned to receive eight cycles of carboplatin plus nab-paclitaxel with or without atezolizumab, followed by surgery and four cycles of an anthracycline-based chemotherapy regimen of the investigators choice.

A total of 280 patients were included in the intention-to-treat (ITT) population, including 138 assigned to receive atezolizumab and 142 who received chemotherapy alone.

Of these groups. 119 and 120, respectively, went on to surgery and were eligible for adjuvant chemotherapy. In all, 79 patients (66%) in the atezolizumab arm and 90 (75%) in the no-atezolizumab arm completed the four planned cycles of postoperative chemotherapy.

At a median follow-up of 54 months, the EFS rate with atezolizumab was 70.6%, compared with 74.9% without atezolizumab, translating into a nonsignificant hazard ratio of 1.076­­ for disease progression while on primary therapy or disease recurrence after surgery, or death from any cause, including unknown causes.

Pathologic complete responses key

In multivariate analysis, significant predictors for better EFS included achievement of a pCR; disease stage (early high risk vs. locally advanced); programmed death ligand-1 (PD-L1) levels above 1% as assessed by the SP142 assay; and higher levels of stromal tumor-infiltrating lymphocytes, but these factors were not predictive of atezolizumab benefit, Dr. Gianni said.

Among all patients who had a pCR, regardless of regimen, the 5-year EFS rate was 90.3%, compared with 55.7% for those who did not receive a pCR, translating into a hazard ratio of 0.19 for pathologic complete responses (P < .0001).

Looking at treatment-related adverse events occurring following surgery – that is, after atezolizumab therapy had stopped – they did not detect any new safety signals. The most common grade 3 or greater toxicity in each arm was neutropenia, followed by leukopenia, and in the atezolizumab arm there was one case of a grade 3 myocarditis that occurred 2 weeks after surgery and before the patient started on an anthracycline.

The authors also conducted a mass cytometry analysis of potential predictors of response to checkpoint inhibitors in TNBC, and reported the results in Nature.

“Basically, baseline density of several activated immune cells predicted for higher probability of pCR with atezolizumab but not with chemotherapy without atezolizumab,” Dr. Gianni said.

Specifically, they saw that high density of CD8-positive, TCF1-positive and Ki-67-positive markers were associated with increased pCR and EFS rates with the addition of atezolizumab.

Why no benefit to the ICI?

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University in Atlanta said that at least two possible explanations floated for the lack of either a pCR or EFS benefit in NeoTRIP don’t hold water.

For example, the theory that a difference in efficacy between PD-1 and PD-L1 inhibitors might explain the lack of benefit in NeoTRIP is undermined by IMpassion031, which showed pCR and EFS benefits with atezolizumab.

In addition, although NeoTRIP did not include an anthracycline in the neoadjuvant regimen, neither did the NeoPACT trial, in which patients received six cycles of neoadjuvant taxane, carboplatin, and pembrolizumab, and had a 58% pCR rate, with a high 2-year EFS rate among patients who had a pCR.

“As we know, triple-negative breast cancer is a heterogeneous disease. Could it be by chance that there are differences in tumor biology reflected across the various neoadjuvant trials, including molecular subtypes? Also in NeoTRIP, previously reported we’ve seen that there were a higher rate of TILs in the chemo-alone arm; high TILs can be associated with chemosensitivity, and maybe this influenced the results,” he said.

Predictive markers to immunotherapy in TNBC are still needed, he said, because neither PD-L1 expression, tumor mutational burden, or TILs have proven to be reliable biomarkers for this subtype.

The NeoTRIP Michelangelo trial was supported by Hoffman-La Roche and Celgene. Dr. Gianni disclosed financial interests with Roche and others including advisory board activity, consulting, and personal fees. Dr. Kalinsky reported advisory/consulting activities for various companies, including Genentech/Roche.

Despite the proven benefit of adding an immune checkpoint inhibitor (ICI) to preoperative chemotherapy for patients with triple-negative breast cancer (TNBC), the NeoTRIP Michelangelo trial stumbled at the finish line, showing that adding atezolizumab (Tecentriq) to nab-paclitaxel and carboplatin followed by surgery and adjuvant anthracycline-based chemotherapy did not improve 5-year event-free survival (EFS), compared with the same regimen without atezolizumab.

Although the trial did not produce the desired result, it still provided important impetus for researchers to do better, said lead investigator Luca Gianni, MD, chair of the international breast cancer research committee at Fondazione Michelangelo in Milan.

“I strongly believe that the results of NeoTRIP, rather than being viewed as negative, should bring forth the search for dependable and widely applicable predictors of ICIs’ benefit in women with operable triple negative breast cancer,” he said in an oral abstract session at the annual meeting of the European Society for Medical Oncology.

Other neoadjuvant trials with different agents have shown benefit from the addition of an ICI to chemotherapy for patients with TNBC, Dr. Gianni noted, with pembrolizumab (Keytruda) in Keynote-522, durvalumab (Imfinzi) in GeparNuevo, and with atezolizumab in IMpassion031.

NeoTRIP results

Dr. Gianni and colleagues had previously reported that adding atezolizumab to neoadjuvant carboplatin/nab-paclitaxel did not significantly improve pathologic complete response rates (pCR) in the randomized trial, although other trials of neoadjuvant ICIs in this population had shown a pCR benefit.

“Our analysis of NeoTRIP supports that pCR may not be an appropriate surrogate endpoint for the role of ICIs in early TNBC,” they wrote in that analysis.

At ESMO 2023, the investigators presented 5-year event-free survival rates, the primary study endpoint, and results of an exploratory analysis of predictive biomarkers.

In the phase 3 trial, patients with HER2-negative, estrogen receptor–negative, and progesterone receptor–negative early high-risk or locally advanced unilateral breast cancer were randomly assigned to receive eight cycles of carboplatin plus nab-paclitaxel with or without atezolizumab, followed by surgery and four cycles of an anthracycline-based chemotherapy regimen of the investigators choice.

A total of 280 patients were included in the intention-to-treat (ITT) population, including 138 assigned to receive atezolizumab and 142 who received chemotherapy alone.

Of these groups. 119 and 120, respectively, went on to surgery and were eligible for adjuvant chemotherapy. In all, 79 patients (66%) in the atezolizumab arm and 90 (75%) in the no-atezolizumab arm completed the four planned cycles of postoperative chemotherapy.

At a median follow-up of 54 months, the EFS rate with atezolizumab was 70.6%, compared with 74.9% without atezolizumab, translating into a nonsignificant hazard ratio of 1.076­­ for disease progression while on primary therapy or disease recurrence after surgery, or death from any cause, including unknown causes.

Pathologic complete responses key

In multivariate analysis, significant predictors for better EFS included achievement of a pCR; disease stage (early high risk vs. locally advanced); programmed death ligand-1 (PD-L1) levels above 1% as assessed by the SP142 assay; and higher levels of stromal tumor-infiltrating lymphocytes, but these factors were not predictive of atezolizumab benefit, Dr. Gianni said.

Among all patients who had a pCR, regardless of regimen, the 5-year EFS rate was 90.3%, compared with 55.7% for those who did not receive a pCR, translating into a hazard ratio of 0.19 for pathologic complete responses (P < .0001).

Looking at treatment-related adverse events occurring following surgery – that is, after atezolizumab therapy had stopped – they did not detect any new safety signals. The most common grade 3 or greater toxicity in each arm was neutropenia, followed by leukopenia, and in the atezolizumab arm there was one case of a grade 3 myocarditis that occurred 2 weeks after surgery and before the patient started on an anthracycline.

The authors also conducted a mass cytometry analysis of potential predictors of response to checkpoint inhibitors in TNBC, and reported the results in Nature.

“Basically, baseline density of several activated immune cells predicted for higher probability of pCR with atezolizumab but not with chemotherapy without atezolizumab,” Dr. Gianni said.

Specifically, they saw that high density of CD8-positive, TCF1-positive and Ki-67-positive markers were associated with increased pCR and EFS rates with the addition of atezolizumab.

Why no benefit to the ICI?

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University in Atlanta said that at least two possible explanations floated for the lack of either a pCR or EFS benefit in NeoTRIP don’t hold water.

For example, the theory that a difference in efficacy between PD-1 and PD-L1 inhibitors might explain the lack of benefit in NeoTRIP is undermined by IMpassion031, which showed pCR and EFS benefits with atezolizumab.

In addition, although NeoTRIP did not include an anthracycline in the neoadjuvant regimen, neither did the NeoPACT trial, in which patients received six cycles of neoadjuvant taxane, carboplatin, and pembrolizumab, and had a 58% pCR rate, with a high 2-year EFS rate among patients who had a pCR.

“As we know, triple-negative breast cancer is a heterogeneous disease. Could it be by chance that there are differences in tumor biology reflected across the various neoadjuvant trials, including molecular subtypes? Also in NeoTRIP, previously reported we’ve seen that there were a higher rate of TILs in the chemo-alone arm; high TILs can be associated with chemosensitivity, and maybe this influenced the results,” he said.

Predictive markers to immunotherapy in TNBC are still needed, he said, because neither PD-L1 expression, tumor mutational burden, or TILs have proven to be reliable biomarkers for this subtype.

The NeoTRIP Michelangelo trial was supported by Hoffman-La Roche and Celgene. Dr. Gianni disclosed financial interests with Roche and others including advisory board activity, consulting, and personal fees. Dr. Kalinsky reported advisory/consulting activities for various companies, including Genentech/Roche.

During treatment for metastatic cancer, remote monitoring of symptoms using electronic patient-reported outcomes (ePROs) reduced health care visits and improved patients’ physical function and quality of life, but did not impact overall survival, according to findings from the PRO-TECT trial.

“Although survival was not impacted in this trial, patients found the intervention to be valuable and experienced improved quality of life and decreased hospitalizations,” said Ethan Basch, MD, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Jiyoung Ahn, PhD, professor of population health at NYU Langone Health and associate director of population science, NYU Langone Perlmutter Cancer Center, both in New York, said this study “provides exciting scientific evidence” supporting real-time, remote monitoring of PROs. Dr. Ahn was not involved with the PRO-TECT trial.

Symptoms among patients with advanced cancer receiving treatment are “exceedingly common,” Dr. Basch explained, but “unfortunately, evidence demonstrates that we as clinicians miss up to 50% of our patients’ symptoms with potential serious downstream consequences.”

Remote monitoring with ePROs can help clinicians detect patients’ symptoms early so they can intervene early.

In the PRO-TECT cluster-randomized trial, 52 oncology practices in the United States were randomly assigned (1:1) to remote monitoring with ePRO surveys or usual care. The cohort included 1,191 patients with metastatic cancer – with 593 patients at PRO practices and 598 patients at control practices. Participating practices could enroll up to 50 patients with any type of metastatic cancer, except for indolent lymphoma or acute leukemia, who were receiving systemic treatment.

Patients in the ePRO practices completed weekly surveys either online or using an automated telephone system for up to 1 year. The survey included questions related to nine common symptoms, performance status, and falls.

For symptoms that are severe or worsening, a real-time alert goes to the care team through the electronic health record or by an email, Dr. Basch explained. Similarly, reports highlighting the longitudinal trajectory of symptoms can be generated at patient visits and reviewed by clinicians, which can bring “the patient and the care team closer together by elevating those issues that are particularly salient to the patient’s experience,” he noted.

Patients completed over 91% of the electronic symptom surveys. After 24 months, the team observed no significant difference in the primary outcome of overall survival – 42.0 months with ePRO vs. 43.5 months with usual care (hazard ratio, 0.99; P = .86).

Dr. Basch and colleagues did, however, observe a 6% reduction in emergency or hospital admissions in the ePRO group, compared with usual care. The ePRO group also had a significantly longer time to first emergency admission (HR, 0.84; P = .03) and a decreased average number of admissions per patient over 1 year (1.48 vs. 1.81; P = .006).

At multiple time points, the team also observed “clinically meaningful and statistically significant” benefits in physical functioning, symptom control, and health-related quality of life, Dr. Basch reported. More patients in the ePRO than the usual-care group experienced benefits in fatigue (odds ratio, 1.77; P < .001), anorexia (OR, 1.32; P = .03), nausea/vomiting (OR, 1.40; P = .01), and sleep (OR, 1.73; P < .001).

Patients’ impressions of the ePRO symptom monitoring system were also “overwhelmingly” positive, Dr. Basch said. Most found the questions relevant and easy to understand and felt that their care team used the information, which made patients feel more in control of their care.

Nurses generally had a favorable impression of the system, with the majority stating that the information was helpful for electronic health record documentation and that it improved discussions with their patients and improved their efficiency.

However, about one-quarter of the nurses expressed reluctance about continuing to use the system, citing the “added work of the ePROs, particularly alerts that were triggered that prompted them to call their patients, particularly during the pandemic when nurses in the United States were pulled in many directions,” Dr. Basch said.

He noted that future ePRO implementations should aim to integrate ePROs into care processes and adjust nurse responsibilities to allow time for ePRO work.

It will also be important to offer a variety of ePRO platforms that are easily accessible for different patient groups. “Notably,” said Dr. Basch, about one-third of the patients selected the automated telephone option. These were largely patients living in rural areas of the United States with lower socioeconomic status and lower health literacy, “suggesting that we need to think about our technologies to meet patients where they are,” he said.

Despite the positive outcomes, there are “challenges to widespread adoption,” agreed NYU’s Dr. Ahn.

These challenges include the need for physician adaptation to new technologies, data security, and ensuring patient engagement and compliance with remote monitoring systems.

“Successfully addressing these challenges is crucial for optimizing the integration of ePROs into cancer care,” Dr. Ahn said.

ESMO’s invited discussant, Anne Letsch, MD, noted that “cancer therapies are getting more complex, and it’s important that patients are well informed and empowered to get together with the treatment teams throughout therapy.”

The high completion rate with ePRO symptom surveys was “quite remarkable,” said Dr. Letsch, head of the Cancer Center at the University Hospital Schleswig Holstein, Kiel, Germany.

But, Dr. Letsch said, it’s “a pity” that there was no overall survival benefit among patients in the ePRO group. Perhaps overall survival is not what matters most in this context, she said. Instead, she asked, “are other outcomes, like health-related quality of life, symptom control and treatment safety, much more important?”

Dr. Basch also questioned whether the survival differences between the two groups may have been blunted because a substantial portion of the trial was conducted during the COVID-19 pandemic, when medical resources and treatments were delayed and diverted.

Dr. Basch pointed to a 2017 study he and colleagues conducted at a single tertiary care medical center, in which patients monitored with ePROs did demonstrate an overall survival benefit, compared with usual care.

Overall, though, the study demonstrated that “symptom monitoring with ePROs is feasible during routine treatment for advanced cancers across diverse practices in the U.S.” and improved patients’ quality of life, Dr. Basch said.

Funding for the study was provided by a grant from the Patient-Centered Outcomes Research Institute. Dr. Basch has disclosed relationships with Resilience Health, Sivan Health, Navigating Cancer, and AstraZeneca. Dr. Letsch and Dr. Ahn report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

During treatment for metastatic cancer, remote monitoring of symptoms using electronic patient-reported outcomes (ePROs) reduced health care visits and improved patients’ physical function and quality of life, but did not impact overall survival, according to findings from the PRO-TECT trial.

“Although survival was not impacted in this trial, patients found the intervention to be valuable and experienced improved quality of life and decreased hospitalizations,” said Ethan Basch, MD, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Jiyoung Ahn, PhD, professor of population health at NYU Langone Health and associate director of population science, NYU Langone Perlmutter Cancer Center, both in New York, said this study “provides exciting scientific evidence” supporting real-time, remote monitoring of PROs. Dr. Ahn was not involved with the PRO-TECT trial.

Symptoms among patients with advanced cancer receiving treatment are “exceedingly common,” Dr. Basch explained, but “unfortunately, evidence demonstrates that we as clinicians miss up to 50% of our patients’ symptoms with potential serious downstream consequences.”

Remote monitoring with ePROs can help clinicians detect patients’ symptoms early so they can intervene early.

In the PRO-TECT cluster-randomized trial, 52 oncology practices in the United States were randomly assigned (1:1) to remote monitoring with ePRO surveys or usual care. The cohort included 1,191 patients with metastatic cancer – with 593 patients at PRO practices and 598 patients at control practices. Participating practices could enroll up to 50 patients with any type of metastatic cancer, except for indolent lymphoma or acute leukemia, who were receiving systemic treatment.

Patients in the ePRO practices completed weekly surveys either online or using an automated telephone system for up to 1 year. The survey included questions related to nine common symptoms, performance status, and falls.

For symptoms that are severe or worsening, a real-time alert goes to the care team through the electronic health record or by an email, Dr. Basch explained. Similarly, reports highlighting the longitudinal trajectory of symptoms can be generated at patient visits and reviewed by clinicians, which can bring “the patient and the care team closer together by elevating those issues that are particularly salient to the patient’s experience,” he noted.

Patients completed over 91% of the electronic symptom surveys. After 24 months, the team observed no significant difference in the primary outcome of overall survival – 42.0 months with ePRO vs. 43.5 months with usual care (hazard ratio, 0.99; P = .86).

Dr. Basch and colleagues did, however, observe a 6% reduction in emergency or hospital admissions in the ePRO group, compared with usual care. The ePRO group also had a significantly longer time to first emergency admission (HR, 0.84; P = .03) and a decreased average number of admissions per patient over 1 year (1.48 vs. 1.81; P = .006).

At multiple time points, the team also observed “clinically meaningful and statistically significant” benefits in physical functioning, symptom control, and health-related quality of life, Dr. Basch reported. More patients in the ePRO than the usual-care group experienced benefits in fatigue (odds ratio, 1.77; P < .001), anorexia (OR, 1.32; P = .03), nausea/vomiting (OR, 1.40; P = .01), and sleep (OR, 1.73; P < .001).

Patients’ impressions of the ePRO symptom monitoring system were also “overwhelmingly” positive, Dr. Basch said. Most found the questions relevant and easy to understand and felt that their care team used the information, which made patients feel more in control of their care.

Nurses generally had a favorable impression of the system, with the majority stating that the information was helpful for electronic health record documentation and that it improved discussions with their patients and improved their efficiency.

However, about one-quarter of the nurses expressed reluctance about continuing to use the system, citing the “added work of the ePROs, particularly alerts that were triggered that prompted them to call their patients, particularly during the pandemic when nurses in the United States were pulled in many directions,” Dr. Basch said.

He noted that future ePRO implementations should aim to integrate ePROs into care processes and adjust nurse responsibilities to allow time for ePRO work.

It will also be important to offer a variety of ePRO platforms that are easily accessible for different patient groups. “Notably,” said Dr. Basch, about one-third of the patients selected the automated telephone option. These were largely patients living in rural areas of the United States with lower socioeconomic status and lower health literacy, “suggesting that we need to think about our technologies to meet patients where they are,” he said.

Despite the positive outcomes, there are “challenges to widespread adoption,” agreed NYU’s Dr. Ahn.

These challenges include the need for physician adaptation to new technologies, data security, and ensuring patient engagement and compliance with remote monitoring systems.

“Successfully addressing these challenges is crucial for optimizing the integration of ePROs into cancer care,” Dr. Ahn said.

ESMO’s invited discussant, Anne Letsch, MD, noted that “cancer therapies are getting more complex, and it’s important that patients are well informed and empowered to get together with the treatment teams throughout therapy.”

The high completion rate with ePRO symptom surveys was “quite remarkable,” said Dr. Letsch, head of the Cancer Center at the University Hospital Schleswig Holstein, Kiel, Germany.

But, Dr. Letsch said, it’s “a pity” that there was no overall survival benefit among patients in the ePRO group. Perhaps overall survival is not what matters most in this context, she said. Instead, she asked, “are other outcomes, like health-related quality of life, symptom control and treatment safety, much more important?”

Dr. Basch also questioned whether the survival differences between the two groups may have been blunted because a substantial portion of the trial was conducted during the COVID-19 pandemic, when medical resources and treatments were delayed and diverted.

Dr. Basch pointed to a 2017 study he and colleagues conducted at a single tertiary care medical center, in which patients monitored with ePROs did demonstrate an overall survival benefit, compared with usual care.

Overall, though, the study demonstrated that “symptom monitoring with ePROs is feasible during routine treatment for advanced cancers across diverse practices in the U.S.” and improved patients’ quality of life, Dr. Basch said.

Funding for the study was provided by a grant from the Patient-Centered Outcomes Research Institute. Dr. Basch has disclosed relationships with Resilience Health, Sivan Health, Navigating Cancer, and AstraZeneca. Dr. Letsch and Dr. Ahn report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

During treatment for metastatic cancer, remote monitoring of symptoms using electronic patient-reported outcomes (ePROs) reduced health care visits and improved patients’ physical function and quality of life, but did not impact overall survival, according to findings from the PRO-TECT trial.

“Although survival was not impacted in this trial, patients found the intervention to be valuable and experienced improved quality of life and decreased hospitalizations,” said Ethan Basch, MD, University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, who presented the findings at the annual meeting of the European Society for Medical Oncology.

Jiyoung Ahn, PhD, professor of population health at NYU Langone Health and associate director of population science, NYU Langone Perlmutter Cancer Center, both in New York, said this study “provides exciting scientific evidence” supporting real-time, remote monitoring of PROs. Dr. Ahn was not involved with the PRO-TECT trial.

Symptoms among patients with advanced cancer receiving treatment are “exceedingly common,” Dr. Basch explained, but “unfortunately, evidence demonstrates that we as clinicians miss up to 50% of our patients’ symptoms with potential serious downstream consequences.”

Remote monitoring with ePROs can help clinicians detect patients’ symptoms early so they can intervene early.

In the PRO-TECT cluster-randomized trial, 52 oncology practices in the United States were randomly assigned (1:1) to remote monitoring with ePRO surveys or usual care. The cohort included 1,191 patients with metastatic cancer – with 593 patients at PRO practices and 598 patients at control practices. Participating practices could enroll up to 50 patients with any type of metastatic cancer, except for indolent lymphoma or acute leukemia, who were receiving systemic treatment.

Patients in the ePRO practices completed weekly surveys either online or using an automated telephone system for up to 1 year. The survey included questions related to nine common symptoms, performance status, and falls.

For symptoms that are severe or worsening, a real-time alert goes to the care team through the electronic health record or by an email, Dr. Basch explained. Similarly, reports highlighting the longitudinal trajectory of symptoms can be generated at patient visits and reviewed by clinicians, which can bring “the patient and the care team closer together by elevating those issues that are particularly salient to the patient’s experience,” he noted.

Patients completed over 91% of the electronic symptom surveys. After 24 months, the team observed no significant difference in the primary outcome of overall survival – 42.0 months with ePRO vs. 43.5 months with usual care (hazard ratio, 0.99; P = .86).

Dr. Basch and colleagues did, however, observe a 6% reduction in emergency or hospital admissions in the ePRO group, compared with usual care. The ePRO group also had a significantly longer time to first emergency admission (HR, 0.84; P = .03) and a decreased average number of admissions per patient over 1 year (1.48 vs. 1.81; P = .006).

At multiple time points, the team also observed “clinically meaningful and statistically significant” benefits in physical functioning, symptom control, and health-related quality of life, Dr. Basch reported. More patients in the ePRO than the usual-care group experienced benefits in fatigue (odds ratio, 1.77; P < .001), anorexia (OR, 1.32; P = .03), nausea/vomiting (OR, 1.40; P = .01), and sleep (OR, 1.73; P < .001).

Patients’ impressions of the ePRO symptom monitoring system were also “overwhelmingly” positive, Dr. Basch said. Most found the questions relevant and easy to understand and felt that their care team used the information, which made patients feel more in control of their care.

Nurses generally had a favorable impression of the system, with the majority stating that the information was helpful for electronic health record documentation and that it improved discussions with their patients and improved their efficiency.

However, about one-quarter of the nurses expressed reluctance about continuing to use the system, citing the “added work of the ePROs, particularly alerts that were triggered that prompted them to call their patients, particularly during the pandemic when nurses in the United States were pulled in many directions,” Dr. Basch said.

He noted that future ePRO implementations should aim to integrate ePROs into care processes and adjust nurse responsibilities to allow time for ePRO work.

It will also be important to offer a variety of ePRO platforms that are easily accessible for different patient groups. “Notably,” said Dr. Basch, about one-third of the patients selected the automated telephone option. These were largely patients living in rural areas of the United States with lower socioeconomic status and lower health literacy, “suggesting that we need to think about our technologies to meet patients where they are,” he said.

Despite the positive outcomes, there are “challenges to widespread adoption,” agreed NYU’s Dr. Ahn.

These challenges include the need for physician adaptation to new technologies, data security, and ensuring patient engagement and compliance with remote monitoring systems.

“Successfully addressing these challenges is crucial for optimizing the integration of ePROs into cancer care,” Dr. Ahn said.

ESMO’s invited discussant, Anne Letsch, MD, noted that “cancer therapies are getting more complex, and it’s important that patients are well informed and empowered to get together with the treatment teams throughout therapy.”

The high completion rate with ePRO symptom surveys was “quite remarkable,” said Dr. Letsch, head of the Cancer Center at the University Hospital Schleswig Holstein, Kiel, Germany.

But, Dr. Letsch said, it’s “a pity” that there was no overall survival benefit among patients in the ePRO group. Perhaps overall survival is not what matters most in this context, she said. Instead, she asked, “are other outcomes, like health-related quality of life, symptom control and treatment safety, much more important?”

Dr. Basch also questioned whether the survival differences between the two groups may have been blunted because a substantial portion of the trial was conducted during the COVID-19 pandemic, when medical resources and treatments were delayed and diverted.

Dr. Basch pointed to a 2017 study he and colleagues conducted at a single tertiary care medical center, in which patients monitored with ePROs did demonstrate an overall survival benefit, compared with usual care.

Overall, though, the study demonstrated that “symptom monitoring with ePROs is feasible during routine treatment for advanced cancers across diverse practices in the U.S.” and improved patients’ quality of life, Dr. Basch said.

Funding for the study was provided by a grant from the Patient-Centered Outcomes Research Institute. Dr. Basch has disclosed relationships with Resilience Health, Sivan Health, Navigating Cancer, and AstraZeneca. Dr. Letsch and Dr. Ahn report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Short-term fasting during chemotherapy enhances health-related quality of life in patients with early breast cancer, with no untoward effects, according to late-breaking research presented on day 1 of the annual meeting of the European Society for Medical Oncology.

“Strikingly,” fasting also appeared to prevent fatigue, something patients with breast cancer struggle with, Daniela A. Koppold, MD, Charité University Medicine Berlin, noted in her oral presentation.

The study adds to other evidence suggesting that fasting around chemotherapy cycles may reduce toxicity and adverse effects associated with chemotherapy.

The invited discussant, Jann Arends, MD, with Freiburg (Germany) University Medical Center, said that the findings fit “very well” with previous observations. “Short-term fasting in subjects not at risk for malnutrition is feasible, well tolerated, and appears to improve several parameters of quality of life,” Dr. Arends said.
 

Promising supportive therapy

The randomized controlled trial assessed the feasibility and impact of short-term fasting on health-related quality of life, compared with a plant-based, low-sugar diet (active comparator) in 106 women with early breast cancer.

The chemotherapy regimens in the trial included four cycles of doxorubicin or epirubicin, followed by taxane therapy. The interventions for both groups occurred about 2 days before chemotherapy plus 24 hours after each cycle ended (about 60-72 hours total).

For the fasting group, this meant about 200 kcal/day through vegetable juices and vegetable broths. In between chemotherapy sessions, both groups were advised to eat a more vegetarian-focused diet, but that was not mandatory.

Health-related quality of life assessments occurred at baseline and after each chemotherapy session (cycle four at day 7) as well as after 4 and 6 months.

The investigators assessed health-related quality of life using the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) that measured the domains of physical, social/familial, emotional, and functional well-being.

At baseline, the two groups had similar FACT-G scores (fasting, 82.9 vs. plant diet, 81.9; P = .523). By day 7, the short-term–fasting group had a significantly better FACT-G score, compared with the plant-based–diet group (fasting, 78.3 vs. plant, 69.5; P = .021).

Although the two groups “started out from the same point, the fasting group had an incremental effect, which quite startled us,” Dr. Koppold told the audience. “Over the course of the chemotherapies, [fasting] had additive effects” and by cycle four of chemotherapy, the difference became statistically and clinically significant, indicating “much better” quality of life in the short-term–fasting group.

What was “even more striking,” said Dr. Koppold, was the impact fasting had on the secondary outcome of fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue).

“Short-term fasting not only had a protective effect on fatigue, compared to the control group, but the short-term–fasting group didn’t develop any clinically visible fatigue,” Dr. Koppold said. “They were in a normal range by cycle four while the control group developed fatigue as we would have expected.”

Importantly, she noted, fasting had no significant impact on weight. The study excluded women who were underweight or had a history of eating disorder or relevant psychopathology.

Summing up, Dr. Koppold said that short-term fasting represents a “promising” supportive therapy during breast cancer chemotherapy to enhance quality of life.

Commenting on the study, Rebecca Guterman, a registered dietitian at Perlmutter Cancer Center at NYU Langone Health, New York, said that it’s well known that a healthy diet plays “a key role during anticancer treatments.” Dietary changes can, for instance, help alleviate common chemotherapy side effects such as loss of appetite, nausea, fatigue, or diarrhea, she said.

These new findings support fasting for 60-72 hours around chemotherapy for some patients with breast cancer who may experience more rapid recovery and better quality of life, said Ms. Guterman.

However, she noted, the results should not be applied to patient populations outside of breast cancer or treatment regimens outside this study. And, she noted, “how the patient feels during the 60-72 hour fast also has to be considered.”

An individual’s “nutritional status must be considered. If a patient has poor appetite and loses weight between treatments, fasting should not be done before next treatment,” Ms. Guterman said.

The study was funded by a private sponsor (G. Müller, Munich, Germany) and a grant from the Günter and Regine KelmFoundation (Zurich). Dr. Koppold is a member of the steering board of ÄGHE e.V. (German-speaking Medical Association for Fasting and Nutrition); cofounder of the Academy for Integrative Fasting GbR; and consults for a mobile app on intermittent fasting (Fastic) as well as a company producing plant-based supplements (EVERYYIN). Dr. Arends has disclosed relationships with Baxter. Ms. Guterman has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Short-term fasting during chemotherapy enhances health-related quality of life in patients with early breast cancer, with no untoward effects, according to late-breaking research presented on day 1 of the annual meeting of the European Society for Medical Oncology.

“Strikingly,” fasting also appeared to prevent fatigue, something patients with breast cancer struggle with, Daniela A. Koppold, MD, Charité University Medicine Berlin, noted in her oral presentation.

The study adds to other evidence suggesting that fasting around chemotherapy cycles may reduce toxicity and adverse effects associated with chemotherapy.

The invited discussant, Jann Arends, MD, with Freiburg (Germany) University Medical Center, said that the findings fit “very well” with previous observations. “Short-term fasting in subjects not at risk for malnutrition is feasible, well tolerated, and appears to improve several parameters of quality of life,” Dr. Arends said.
 

Promising supportive therapy

The randomized controlled trial assessed the feasibility and impact of short-term fasting on health-related quality of life, compared with a plant-based, low-sugar diet (active comparator) in 106 women with early breast cancer.

The chemotherapy regimens in the trial included four cycles of doxorubicin or epirubicin, followed by taxane therapy. The interventions for both groups occurred about 2 days before chemotherapy plus 24 hours after each cycle ended (about 60-72 hours total).

For the fasting group, this meant about 200 kcal/day through vegetable juices and vegetable broths. In between chemotherapy sessions, both groups were advised to eat a more vegetarian-focused diet, but that was not mandatory.

Health-related quality of life assessments occurred at baseline and after each chemotherapy session (cycle four at day 7) as well as after 4 and 6 months.

The investigators assessed health-related quality of life using the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) that measured the domains of physical, social/familial, emotional, and functional well-being.

At baseline, the two groups had similar FACT-G scores (fasting, 82.9 vs. plant diet, 81.9; P = .523). By day 7, the short-term–fasting group had a significantly better FACT-G score, compared with the plant-based–diet group (fasting, 78.3 vs. plant, 69.5; P = .021).

Although the two groups “started out from the same point, the fasting group had an incremental effect, which quite startled us,” Dr. Koppold told the audience. “Over the course of the chemotherapies, [fasting] had additive effects” and by cycle four of chemotherapy, the difference became statistically and clinically significant, indicating “much better” quality of life in the short-term–fasting group.

What was “even more striking,” said Dr. Koppold, was the impact fasting had on the secondary outcome of fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue).

“Short-term fasting not only had a protective effect on fatigue, compared to the control group, but the short-term–fasting group didn’t develop any clinically visible fatigue,” Dr. Koppold said. “They were in a normal range by cycle four while the control group developed fatigue as we would have expected.”

Importantly, she noted, fasting had no significant impact on weight. The study excluded women who were underweight or had a history of eating disorder or relevant psychopathology.

Summing up, Dr. Koppold said that short-term fasting represents a “promising” supportive therapy during breast cancer chemotherapy to enhance quality of life.

Commenting on the study, Rebecca Guterman, a registered dietitian at Perlmutter Cancer Center at NYU Langone Health, New York, said that it’s well known that a healthy diet plays “a key role during anticancer treatments.” Dietary changes can, for instance, help alleviate common chemotherapy side effects such as loss of appetite, nausea, fatigue, or diarrhea, she said.

These new findings support fasting for 60-72 hours around chemotherapy for some patients with breast cancer who may experience more rapid recovery and better quality of life, said Ms. Guterman.

However, she noted, the results should not be applied to patient populations outside of breast cancer or treatment regimens outside this study. And, she noted, “how the patient feels during the 60-72 hour fast also has to be considered.”

An individual’s “nutritional status must be considered. If a patient has poor appetite and loses weight between treatments, fasting should not be done before next treatment,” Ms. Guterman said.

The study was funded by a private sponsor (G. Müller, Munich, Germany) and a grant from the Günter and Regine KelmFoundation (Zurich). Dr. Koppold is a member of the steering board of ÄGHE e.V. (German-speaking Medical Association for Fasting and Nutrition); cofounder of the Academy for Integrative Fasting GbR; and consults for a mobile app on intermittent fasting (Fastic) as well as a company producing plant-based supplements (EVERYYIN). Dr. Arends has disclosed relationships with Baxter. Ms. Guterman has no relevant disclosures.

A version of this article first appeared on Medscape.com.

Short-term fasting during chemotherapy enhances health-related quality of life in patients with early breast cancer, with no untoward effects, according to late-breaking research presented on day 1 of the annual meeting of the European Society for Medical Oncology.

“Strikingly,” fasting also appeared to prevent fatigue, something patients with breast cancer struggle with, Daniela A. Koppold, MD, Charité University Medicine Berlin, noted in her oral presentation.

The study adds to other evidence suggesting that fasting around chemotherapy cycles may reduce toxicity and adverse effects associated with chemotherapy.

The invited discussant, Jann Arends, MD, with Freiburg (Germany) University Medical Center, said that the findings fit “very well” with previous observations. “Short-term fasting in subjects not at risk for malnutrition is feasible, well tolerated, and appears to improve several parameters of quality of life,” Dr. Arends said.
 

Promising supportive therapy

The randomized controlled trial assessed the feasibility and impact of short-term fasting on health-related quality of life, compared with a plant-based, low-sugar diet (active comparator) in 106 women with early breast cancer.

The chemotherapy regimens in the trial included four cycles of doxorubicin or epirubicin, followed by taxane therapy. The interventions for both groups occurred about 2 days before chemotherapy plus 24 hours after each cycle ended (about 60-72 hours total).

For the fasting group, this meant about 200 kcal/day through vegetable juices and vegetable broths. In between chemotherapy sessions, both groups were advised to eat a more vegetarian-focused diet, but that was not mandatory.

Health-related quality of life assessments occurred at baseline and after each chemotherapy session (cycle four at day 7) as well as after 4 and 6 months.

The investigators assessed health-related quality of life using the 27-item Functional Assessment of Cancer Therapy-General (FACT-G) that measured the domains of physical, social/familial, emotional, and functional well-being.

At baseline, the two groups had similar FACT-G scores (fasting, 82.9 vs. plant diet, 81.9; P = .523). By day 7, the short-term–fasting group had a significantly better FACT-G score, compared with the plant-based–diet group (fasting, 78.3 vs. plant, 69.5; P = .021).

Although the two groups “started out from the same point, the fasting group had an incremental effect, which quite startled us,” Dr. Koppold told the audience. “Over the course of the chemotherapies, [fasting] had additive effects” and by cycle four of chemotherapy, the difference became statistically and clinically significant, indicating “much better” quality of life in the short-term–fasting group.

What was “even more striking,” said Dr. Koppold, was the impact fasting had on the secondary outcome of fatigue (Functional Assessment of Chronic Illness Therapy–Fatigue).

“Short-term fasting not only had a protective effect on fatigue, compared to the control group, but the short-term–fasting group didn’t develop any clinically visible fatigue,” Dr. Koppold said. “They were in a normal range by cycle four while the control group developed fatigue as we would have expected.”

Importantly, she noted, fasting had no significant impact on weight. The study excluded women who were underweight or had a history of eating disorder or relevant psychopathology.

Summing up, Dr. Koppold said that short-term fasting represents a “promising” supportive therapy during breast cancer chemotherapy to enhance quality of life.

Commenting on the study, Rebecca Guterman, a registered dietitian at Perlmutter Cancer Center at NYU Langone Health, New York, said that it’s well known that a healthy diet plays “a key role during anticancer treatments.” Dietary changes can, for instance, help alleviate common chemotherapy side effects such as loss of appetite, nausea, fatigue, or diarrhea, she said.

These new findings support fasting for 60-72 hours around chemotherapy for some patients with breast cancer who may experience more rapid recovery and better quality of life, said Ms. Guterman.

However, she noted, the results should not be applied to patient populations outside of breast cancer or treatment regimens outside this study. And, she noted, “how the patient feels during the 60-72 hour fast also has to be considered.”

An individual’s “nutritional status must be considered. If a patient has poor appetite and loses weight between treatments, fasting should not be done before next treatment,” Ms. Guterman said.

The study was funded by a private sponsor (G. Müller, Munich, Germany) and a grant from the Günter and Regine KelmFoundation (Zurich). Dr. Koppold is a member of the steering board of ÄGHE e.V. (German-speaking Medical Association for Fasting and Nutrition); cofounder of the Academy for Integrative Fasting GbR; and consults for a mobile app on intermittent fasting (Fastic) as well as a company producing plant-based supplements (EVERYYIN). Dr. Arends has disclosed relationships with Baxter. Ms. Guterman has no relevant disclosures.

A version of this article first appeared on Medscape.com.

MADRID – Five years on, the addition of the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy for women with high-risk hormone receptor–positive, HER2-negative (HR+/HER2–) early breast cancer continues to show modest but clinically significant benefits, compared with endocrine therapy alone.

Results of a planned 5-year efficacy analysis of the monarchE trial showed that at a median follow-up of 4.5 years, the abemaciclib/endocrine therapy combination was associated with a 7.6% absolute improvement in invasive disease–free survival (IDFS) and 6.7% edge in distant relapse–free survival (DRFS), compared with endocrine therapy alone, reported Nadia Harbeck, MD, from the Breast Center at Ludwig Maximilians University Hospital in Munich.

“The data are consistent with a carryover effect and further support the addition of adjuvant abemaciclib to endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive high-risk early breast cancer,” she said at the 2023 European Society for Medical Oncology Congress.
 

High recurrence risk

Although HR+/HER2– breast cancer, the most common subtype of breast cancer, is generally associated with better outcomes than other subtypes, patients with node-positive early disease are at high risk for early recurrence and need treatment intensification, Dr. Harbeck said.

The monarchE trial included two cohorts: a primary cohort consisting of patients deemed at high risk based on clinical pathological features such as the number of involved axillary nodes, grade 3 disease, and tumors 5 cm or larger, and a second cohort of patients with lower disease grade and smaller tumors but with high levels of the proliferation marker Ki-67.

A total of 5,637 patients were randomized to receive either 2 years of abemaciclib 150 mg twice daily plus endocrine therapy, or endocrine therapy alone, followed by 3-8 years of additional endocrine as clinically indicated in each study arm.

An earlier preplanned interim analysis of the phase 3 trial of more than 5,600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.

As that analysis showed, at a median follow-up of 15.5 months abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of IDFS vs. endocrine therapy alone.

At the time, the findings were hailed as practice-changing and, once approved for high-risk HR+/HER2-negative early breast cancer, as the new standard of care.

In the current analysis, Dr. Harbeck and colleagues looked at 5-year outcomes from a prespecified analysis, with a data cutoff of July 3, 2023.

All patients originally assigned to abemaciclib are now off the drug, and more than 80% have been followed for a minimum of 2 year since completing therapy with the CDK4/6 inhibitor.
 

Results

At 5 years there were cumulative totals of 407 IDFS events in the combination arm, compared with 585 in the endocrine therapy alone arm, a difference that translated into a hazard ratio of 0.68 favoring abemaciclib (P < .001).

The IDFS benefit with the combination was consistent across most subgroups, including older patients, perimenopausal and postmenopausal patients, those who had received prior neoadjuvant or adjuvant chemotherapy, all tumor sizes, number of positive lymph nodes, less favorable tumor stage or grade, and order of endocrine therapy (tamoxifen or aromatase inhibitor as first drug).

As noted before, DRFS, a secondary endpoint, also favored abemaciclib, with 345 events occurring over 5 years in the combination arm, compared with 501 in the endocrine therapy arm alone. This translated into a HR with the combination of 0.68 (P < .001).

There were fewer deaths in the abemaciclib arm (208 vs. 234), but this difference was not statistically significant.

The proportions of patients with treatment-emergent adverse events and serious adverse events (SAEs) were higher in the combination arm than in the endocrine therapy alone arm in all previous analyses of the trial data.

In the current analysis, “I would say it’s reassuring to see that the SAEs reported in the follow-up period, after the study treatment had been completed, are quite similar between the endocrine therapy alone arm and the abemaciclib plus endocrine therapy arm,” Dr. Harbeck said.
 

Changing road map

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University, Atlanta, commented that CDK4/6 inhibitors “have changed the road map for treating hormone receptor–positive, HER2-negative disease.”

To put the monarchE results in context, he compared them with those of the NATALEE trial, in which patients were randomized to endocrine therapy with or without the CDK4/6 inhibitor ribociclib (Kisqali). That combination was previously shown to provide a significant survival advantage for women with metastatic breast cancer.

In NATALEE, which included both high-risk and intermediate-risk patients with early breast cancer, the absolute difference in 3-year IDFS rates between the combination group and endocrine monotherapy groups was 3.3%.

To determine the ultimate value of combining a CDK4/6 inhibitor with endocrine therapy in early breast cancer, longer follow-up of both trials will be necessary, Dr. Kalinsky said.

“The reason that follow-up is critical for both of these studies is that for this subtype of breast cancer, based upon data including from the Early Breast Cancer Trialists Group, we can see approximately 50% of recurrences after the first 5 years, and we think of cytotoxic chemotherapy as benefiting patients within those first 5 years. And while we think of CDK4/6 inhibitors as being cytostatic drugs, we are seeing a carryover effect in which 2 years of abemaciclib is improving outcome at the 5-year landmark,” he said.

Questions that still need to be answered include the optimal duration of CDK4/6 inhibitor therapy, whether adjuvant therapy should be resumed when there are signs of renewed proliferation, and whether there would be a benefit to restarting CDK4/6 inhibitors when metastasis occurs.

The monarchE trial was sponsored by Eli Lilly and Co. Dr. Harbeck disclosed research funding and speaker’s bureau activity for Lilly and others, and a consulting or advisory role with Gilead, Roche, Sanofi, Sandoz, and Seagen. Dr. Kalinsky disclosed a consulting or advisory role with multiple companies, not including Lilly.

MADRID – Five years on, the addition of the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy for women with high-risk hormone receptor–positive, HER2-negative (HR+/HER2–) early breast cancer continues to show modest but clinically significant benefits, compared with endocrine therapy alone.

Results of a planned 5-year efficacy analysis of the monarchE trial showed that at a median follow-up of 4.5 years, the abemaciclib/endocrine therapy combination was associated with a 7.6% absolute improvement in invasive disease–free survival (IDFS) and 6.7% edge in distant relapse–free survival (DRFS), compared with endocrine therapy alone, reported Nadia Harbeck, MD, from the Breast Center at Ludwig Maximilians University Hospital in Munich.

“The data are consistent with a carryover effect and further support the addition of adjuvant abemaciclib to endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive high-risk early breast cancer,” she said at the 2023 European Society for Medical Oncology Congress.
 

High recurrence risk

Although HR+/HER2– breast cancer, the most common subtype of breast cancer, is generally associated with better outcomes than other subtypes, patients with node-positive early disease are at high risk for early recurrence and need treatment intensification, Dr. Harbeck said.

The monarchE trial included two cohorts: a primary cohort consisting of patients deemed at high risk based on clinical pathological features such as the number of involved axillary nodes, grade 3 disease, and tumors 5 cm or larger, and a second cohort of patients with lower disease grade and smaller tumors but with high levels of the proliferation marker Ki-67.

A total of 5,637 patients were randomized to receive either 2 years of abemaciclib 150 mg twice daily plus endocrine therapy, or endocrine therapy alone, followed by 3-8 years of additional endocrine as clinically indicated in each study arm.

An earlier preplanned interim analysis of the phase 3 trial of more than 5,600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.

As that analysis showed, at a median follow-up of 15.5 months abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of IDFS vs. endocrine therapy alone.

At the time, the findings were hailed as practice-changing and, once approved for high-risk HR+/HER2-negative early breast cancer, as the new standard of care.

In the current analysis, Dr. Harbeck and colleagues looked at 5-year outcomes from a prespecified analysis, with a data cutoff of July 3, 2023.

All patients originally assigned to abemaciclib are now off the drug, and more than 80% have been followed for a minimum of 2 year since completing therapy with the CDK4/6 inhibitor.
 

Results

At 5 years there were cumulative totals of 407 IDFS events in the combination arm, compared with 585 in the endocrine therapy alone arm, a difference that translated into a hazard ratio of 0.68 favoring abemaciclib (P < .001).

The IDFS benefit with the combination was consistent across most subgroups, including older patients, perimenopausal and postmenopausal patients, those who had received prior neoadjuvant or adjuvant chemotherapy, all tumor sizes, number of positive lymph nodes, less favorable tumor stage or grade, and order of endocrine therapy (tamoxifen or aromatase inhibitor as first drug).

As noted before, DRFS, a secondary endpoint, also favored abemaciclib, with 345 events occurring over 5 years in the combination arm, compared with 501 in the endocrine therapy arm alone. This translated into a HR with the combination of 0.68 (P < .001).

There were fewer deaths in the abemaciclib arm (208 vs. 234), but this difference was not statistically significant.

The proportions of patients with treatment-emergent adverse events and serious adverse events (SAEs) were higher in the combination arm than in the endocrine therapy alone arm in all previous analyses of the trial data.

In the current analysis, “I would say it’s reassuring to see that the SAEs reported in the follow-up period, after the study treatment had been completed, are quite similar between the endocrine therapy alone arm and the abemaciclib plus endocrine therapy arm,” Dr. Harbeck said.
 

Changing road map

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University, Atlanta, commented that CDK4/6 inhibitors “have changed the road map for treating hormone receptor–positive, HER2-negative disease.”

To put the monarchE results in context, he compared them with those of the NATALEE trial, in which patients were randomized to endocrine therapy with or without the CDK4/6 inhibitor ribociclib (Kisqali). That combination was previously shown to provide a significant survival advantage for women with metastatic breast cancer.

In NATALEE, which included both high-risk and intermediate-risk patients with early breast cancer, the absolute difference in 3-year IDFS rates between the combination group and endocrine monotherapy groups was 3.3%.

To determine the ultimate value of combining a CDK4/6 inhibitor with endocrine therapy in early breast cancer, longer follow-up of both trials will be necessary, Dr. Kalinsky said.

“The reason that follow-up is critical for both of these studies is that for this subtype of breast cancer, based upon data including from the Early Breast Cancer Trialists Group, we can see approximately 50% of recurrences after the first 5 years, and we think of cytotoxic chemotherapy as benefiting patients within those first 5 years. And while we think of CDK4/6 inhibitors as being cytostatic drugs, we are seeing a carryover effect in which 2 years of abemaciclib is improving outcome at the 5-year landmark,” he said.

Questions that still need to be answered include the optimal duration of CDK4/6 inhibitor therapy, whether adjuvant therapy should be resumed when there are signs of renewed proliferation, and whether there would be a benefit to restarting CDK4/6 inhibitors when metastasis occurs.

The monarchE trial was sponsored by Eli Lilly and Co. Dr. Harbeck disclosed research funding and speaker’s bureau activity for Lilly and others, and a consulting or advisory role with Gilead, Roche, Sanofi, Sandoz, and Seagen. Dr. Kalinsky disclosed a consulting or advisory role with multiple companies, not including Lilly.

MADRID – Five years on, the addition of the CDK4/6 inhibitor abemaciclib (Verzenio) to endocrine therapy for women with high-risk hormone receptor–positive, HER2-negative (HR+/HER2–) early breast cancer continues to show modest but clinically significant benefits, compared with endocrine therapy alone.

Results of a planned 5-year efficacy analysis of the monarchE trial showed that at a median follow-up of 4.5 years, the abemaciclib/endocrine therapy combination was associated with a 7.6% absolute improvement in invasive disease–free survival (IDFS) and 6.7% edge in distant relapse–free survival (DRFS), compared with endocrine therapy alone, reported Nadia Harbeck, MD, from the Breast Center at Ludwig Maximilians University Hospital in Munich.

“The data are consistent with a carryover effect and further support the addition of adjuvant abemaciclib to endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive high-risk early breast cancer,” she said at the 2023 European Society for Medical Oncology Congress.
 

High recurrence risk

Although HR+/HER2– breast cancer, the most common subtype of breast cancer, is generally associated with better outcomes than other subtypes, patients with node-positive early disease are at high risk for early recurrence and need treatment intensification, Dr. Harbeck said.

The monarchE trial included two cohorts: a primary cohort consisting of patients deemed at high risk based on clinical pathological features such as the number of involved axillary nodes, grade 3 disease, and tumors 5 cm or larger, and a second cohort of patients with lower disease grade and smaller tumors but with high levels of the proliferation marker Ki-67.

A total of 5,637 patients were randomized to receive either 2 years of abemaciclib 150 mg twice daily plus endocrine therapy, or endocrine therapy alone, followed by 3-8 years of additional endocrine as clinically indicated in each study arm.

An earlier preplanned interim analysis of the phase 3 trial of more than 5,600 patients was presented at the ESMO Virtual Congress 2020, and simultaneously published in the Journal of Clinical Oncology.

As that analysis showed, at a median follow-up of 15.5 months abemaciclib plus endocrine therapy was associated with a 25% relative risk reduction in the primary endpoint of IDFS vs. endocrine therapy alone.

At the time, the findings were hailed as practice-changing and, once approved for high-risk HR+/HER2-negative early breast cancer, as the new standard of care.

In the current analysis, Dr. Harbeck and colleagues looked at 5-year outcomes from a prespecified analysis, with a data cutoff of July 3, 2023.

All patients originally assigned to abemaciclib are now off the drug, and more than 80% have been followed for a minimum of 2 year since completing therapy with the CDK4/6 inhibitor.
 

Results

At 5 years there were cumulative totals of 407 IDFS events in the combination arm, compared with 585 in the endocrine therapy alone arm, a difference that translated into a hazard ratio of 0.68 favoring abemaciclib (P < .001).

The IDFS benefit with the combination was consistent across most subgroups, including older patients, perimenopausal and postmenopausal patients, those who had received prior neoadjuvant or adjuvant chemotherapy, all tumor sizes, number of positive lymph nodes, less favorable tumor stage or grade, and order of endocrine therapy (tamoxifen or aromatase inhibitor as first drug).

As noted before, DRFS, a secondary endpoint, also favored abemaciclib, with 345 events occurring over 5 years in the combination arm, compared with 501 in the endocrine therapy arm alone. This translated into a HR with the combination of 0.68 (P < .001).

There were fewer deaths in the abemaciclib arm (208 vs. 234), but this difference was not statistically significant.

The proportions of patients with treatment-emergent adverse events and serious adverse events (SAEs) were higher in the combination arm than in the endocrine therapy alone arm in all previous analyses of the trial data.

In the current analysis, “I would say it’s reassuring to see that the SAEs reported in the follow-up period, after the study treatment had been completed, are quite similar between the endocrine therapy alone arm and the abemaciclib plus endocrine therapy arm,” Dr. Harbeck said.
 

Changing road map

Invited discussant Kevin Kalinsky, MD, MS, from the Winship Cancer Institute at Emory University, Atlanta, commented that CDK4/6 inhibitors “have changed the road map for treating hormone receptor–positive, HER2-negative disease.”

To put the monarchE results in context, he compared them with those of the NATALEE trial, in which patients were randomized to endocrine therapy with or without the CDK4/6 inhibitor ribociclib (Kisqali). That combination was previously shown to provide a significant survival advantage for women with metastatic breast cancer.

In NATALEE, which included both high-risk and intermediate-risk patients with early breast cancer, the absolute difference in 3-year IDFS rates between the combination group and endocrine monotherapy groups was 3.3%.

To determine the ultimate value of combining a CDK4/6 inhibitor with endocrine therapy in early breast cancer, longer follow-up of both trials will be necessary, Dr. Kalinsky said.

“The reason that follow-up is critical for both of these studies is that for this subtype of breast cancer, based upon data including from the Early Breast Cancer Trialists Group, we can see approximately 50% of recurrences after the first 5 years, and we think of cytotoxic chemotherapy as benefiting patients within those first 5 years. And while we think of CDK4/6 inhibitors as being cytostatic drugs, we are seeing a carryover effect in which 2 years of abemaciclib is improving outcome at the 5-year landmark,” he said.

Questions that still need to be answered include the optimal duration of CDK4/6 inhibitor therapy, whether adjuvant therapy should be resumed when there are signs of renewed proliferation, and whether there would be a benefit to restarting CDK4/6 inhibitors when metastasis occurs.

The monarchE trial was sponsored by Eli Lilly and Co. Dr. Harbeck disclosed research funding and speaker’s bureau activity for Lilly and others, and a consulting or advisory role with Gilead, Roche, Sanofi, Sandoz, and Seagen. Dr. Kalinsky disclosed a consulting or advisory role with multiple companies, not including Lilly.

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com

The Food and Drug Administration is considering banning chemicals used in hair straightening products that have been linked to cancer.

The proposal specifies that formaldehyde would be banned, as well as other chemicals that release formaldehyde, such as methylene glycol. Using hair smoothing products containing formaldehyde and formaldehyde-releasing chemicals “is linked to short-term adverse health effects, such as sensitization reactions and breathing problems, and long-term adverse health effects, including an increased risk of certain cancers,” the proposal states.

One study published last year showed that repeated use of hair straightening products, also called relaxers, could more than double the risk of uterine cancer. Although that study didn’t find that the uterine cancer risk varied based on a person’s race, the researchers noted that women who are Black are among the most likely to use the products and tend to start using them at younger ages, compared with people of other races and ethnicities.

Hair straightening products have also been linked to elevated risks of hormone-sensitive cancers, such as breast cancer and ovarian cancer.

Rep. Ayanna Pressley (D-Mass.) and Rep. Shontel Brown (D-Ohio) applauded the proposed rule in a statement issued jointly on Oct. 6. “The FDA’s proposal to ban these harmful chemicals in hair straighteners and relaxers is a win for public health – especially the health of Black women who are disproportionately put at risk by these products as a result of systemic racism and anti–Black hair sentiment,” Rep. Pressley said The two congresswomen wrote a letter to the FDA earlier this year requesting the topic be investigated.

“Regardless of how we wear our hair, we should be allowed to show up in the world without putting our health at risk. I applaud the FDA for being responsive to our calls and advancing a rule that will help prevent manufacturers from making a profit at the expense of our health,” Rep. Pressley said in the statement. “The administration should finalize this rule without delay.”



A version of this article appeared on WebMD.com