Will Pass

SAN ANTONIO – For patients with newly diagnosed HER2-negative breast cancer who are BRCA carriers, neoadjuvant cisplatin does not offer a higher pathologic complete response (pCR) rate than standard doxorubicin/cyclophosphamide (AC), based on results from the phase 2 INFORM trial.

Will Pass/MDedge News

Findings from this trial and others suggest that BRCA deficiency may be a marker of sensitivity to DNA-damaging chemotherapy generally, instead of platinum agents specifically, reported lead author Nadine Tung, MD, of Beth Israel Deaconess Medical Center in Boston.

While single-agent platinum chemotherapy has shown significant clinical activity in the neoadjuvant and metastatic settings for BRCA-mutated triple-negative breast cancer (TNBC), prospective trials comparing platinum-based therapy with non–platinum-based therapy have been lacking, Dr. Tung said during a presentation at the San Antonio Breast Cancer Symposium.

“Almost no data exist for the response to platinum agents among BRCA carriers with hormone receptor–positive breast cancer,” Dr. Tung said.

The investigators aimed to address both of these knowledge gaps with a head-to-head trial. Although the investigators aimed for an accrual of 170 participants, all newly diagnosed patients, only 118 were enrolled, of whom 117 were included in the final analysis. All patients had HER2-negative breast cancer with at least one germline BRCA mutation. About two-thirds of patients (69%) were BRCA1 positive, about one-third (30%) were BRCA2 positive, and the small remainder (2%) had both mutations. Clinical stage proportions were as follows: I (19%), II (63%), and III (18%). Almost three-fourths of patients (70%) had TNBC, and 45% had nodal involvement upon enrollment.

Patients were randomized at a 1:1 ratio to receive either cisplatin (75 mg/m² every 3 weeks for four cycles) or standard AC (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² every 2-3 weeks for four cycles). These treatments were followed by surgery. The primary endpoint was pCR . Secondary endpoints included residual cancer burden of 0-1 (RCB 0/1), 3-year disease-free survival, and toxicities.

Most patients completed the regimens as planned; however, seven patients received more than four cycles of chemotherapy while four patients completed fewer than four cycles. These 11 patients were categorized as not having a pathologic complete response.

Among the remaining patients, platinum-based chemotherapy was associated with an 18% pCR rate, compared with 26% for standard AC, which translated to a risk ratio of 0.70 that was not significant. Among patients with TNBC (n = 82), pCR rates followed a similar trend (22% vs. 28%), again without statistical significance. For patients with estrogen receptor–positive disease, the numerical disparity in pCR rate was greater (cisplatin at 6% vs. AC at 21%); however, once more, this difference was not statistically significant. Because of the small number of patients in this subgroup (n = 35), Dr. Tung advised that results be interpreted with caution.

Results for RCB 0/1 were similar to pCR. AC was associated with a higher rate of RCB 0-1 for all patients (46% vs. 33%), patients with TNBC (47% vs. 36%), and patients with hormone receptor–positive disease (42% vs. 25%). Across all patients and subtypes, these differences were not statistically significant.

Safety profiles were similar to previously published data for both regimens.

“In conclusion, contrary to our initial expectations, the pCR rate and RCB 0/1 rate is not significantly higher after cisplatin than after AC in BRCA carriers with early-stage breast cancer, whether triple-negative or estrogen receptor–positive HER2-negative disease,” Dr. Tung said. “Our statistician has concluded that there is no realistic scenario by which the pCR with cisplatin would have been significantly higher than with AC had this study met its accrual.”

“We believe the results of the INFORM trial are consistent with those of the GeparSixto and BrightTNess neoadjuvant trials,” Dr. Tung said. “One interpretation of the INFORM trial results, as well as these two trials, is that breast cancer in BRCA carriers is more sensitive than in noncarriers to DNA-damaging agents. … BRCA deficiency or homologous combination deficiency may simply be a marker of sensitivity to DNA-damaging chemotherapy rather than platinum agents specifically.”

The investigators disclosed relationships with Merck, AstraZeneca, Genentech, and others.

SOURCE: Tung N et al. SABCS 2019, Abstract GS6-03.

SAN ANTONIO – For patients with newly diagnosed HER2-negative breast cancer who are BRCA carriers, neoadjuvant cisplatin does not offer a higher pathologic complete response (pCR) rate than standard doxorubicin/cyclophosphamide (AC), based on results from the phase 2 INFORM trial.

Will Pass/MDedge News

Findings from this trial and others suggest that BRCA deficiency may be a marker of sensitivity to DNA-damaging chemotherapy generally, instead of platinum agents specifically, reported lead author Nadine Tung, MD, of Beth Israel Deaconess Medical Center in Boston.

While single-agent platinum chemotherapy has shown significant clinical activity in the neoadjuvant and metastatic settings for BRCA-mutated triple-negative breast cancer (TNBC), prospective trials comparing platinum-based therapy with non–platinum-based therapy have been lacking, Dr. Tung said during a presentation at the San Antonio Breast Cancer Symposium.

“Almost no data exist for the response to platinum agents among BRCA carriers with hormone receptor–positive breast cancer,” Dr. Tung said.

The investigators aimed to address both of these knowledge gaps with a head-to-head trial. Although the investigators aimed for an accrual of 170 participants, all newly diagnosed patients, only 118 were enrolled, of whom 117 were included in the final analysis. All patients had HER2-negative breast cancer with at least one germline BRCA mutation. About two-thirds of patients (69%) were BRCA1 positive, about one-third (30%) were BRCA2 positive, and the small remainder (2%) had both mutations. Clinical stage proportions were as follows: I (19%), II (63%), and III (18%). Almost three-fourths of patients (70%) had TNBC, and 45% had nodal involvement upon enrollment.

Patients were randomized at a 1:1 ratio to receive either cisplatin (75 mg/m² every 3 weeks for four cycles) or standard AC (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² every 2-3 weeks for four cycles). These treatments were followed by surgery. The primary endpoint was pCR . Secondary endpoints included residual cancer burden of 0-1 (RCB 0/1), 3-year disease-free survival, and toxicities.

Most patients completed the regimens as planned; however, seven patients received more than four cycles of chemotherapy while four patients completed fewer than four cycles. These 11 patients were categorized as not having a pathologic complete response.

Among the remaining patients, platinum-based chemotherapy was associated with an 18% pCR rate, compared with 26% for standard AC, which translated to a risk ratio of 0.70 that was not significant. Among patients with TNBC (n = 82), pCR rates followed a similar trend (22% vs. 28%), again without statistical significance. For patients with estrogen receptor–positive disease, the numerical disparity in pCR rate was greater (cisplatin at 6% vs. AC at 21%); however, once more, this difference was not statistically significant. Because of the small number of patients in this subgroup (n = 35), Dr. Tung advised that results be interpreted with caution.

Results for RCB 0/1 were similar to pCR. AC was associated with a higher rate of RCB 0-1 for all patients (46% vs. 33%), patients with TNBC (47% vs. 36%), and patients with hormone receptor–positive disease (42% vs. 25%). Across all patients and subtypes, these differences were not statistically significant.

Safety profiles were similar to previously published data for both regimens.

“In conclusion, contrary to our initial expectations, the pCR rate and RCB 0/1 rate is not significantly higher after cisplatin than after AC in BRCA carriers with early-stage breast cancer, whether triple-negative or estrogen receptor–positive HER2-negative disease,” Dr. Tung said. “Our statistician has concluded that there is no realistic scenario by which the pCR with cisplatin would have been significantly higher than with AC had this study met its accrual.”

“We believe the results of the INFORM trial are consistent with those of the GeparSixto and BrightTNess neoadjuvant trials,” Dr. Tung said. “One interpretation of the INFORM trial results, as well as these two trials, is that breast cancer in BRCA carriers is more sensitive than in noncarriers to DNA-damaging agents. … BRCA deficiency or homologous combination deficiency may simply be a marker of sensitivity to DNA-damaging chemotherapy rather than platinum agents specifically.”

The investigators disclosed relationships with Merck, AstraZeneca, Genentech, and others.

SOURCE: Tung N et al. SABCS 2019, Abstract GS6-03.

SAN ANTONIO – For patients with newly diagnosed HER2-negative breast cancer who are BRCA carriers, neoadjuvant cisplatin does not offer a higher pathologic complete response (pCR) rate than standard doxorubicin/cyclophosphamide (AC), based on results from the phase 2 INFORM trial.

Will Pass/MDedge News

Findings from this trial and others suggest that BRCA deficiency may be a marker of sensitivity to DNA-damaging chemotherapy generally, instead of platinum agents specifically, reported lead author Nadine Tung, MD, of Beth Israel Deaconess Medical Center in Boston.

While single-agent platinum chemotherapy has shown significant clinical activity in the neoadjuvant and metastatic settings for BRCA-mutated triple-negative breast cancer (TNBC), prospective trials comparing platinum-based therapy with non–platinum-based therapy have been lacking, Dr. Tung said during a presentation at the San Antonio Breast Cancer Symposium.

“Almost no data exist for the response to platinum agents among BRCA carriers with hormone receptor–positive breast cancer,” Dr. Tung said.

The investigators aimed to address both of these knowledge gaps with a head-to-head trial. Although the investigators aimed for an accrual of 170 participants, all newly diagnosed patients, only 118 were enrolled, of whom 117 were included in the final analysis. All patients had HER2-negative breast cancer with at least one germline BRCA mutation. About two-thirds of patients (69%) were BRCA1 positive, about one-third (30%) were BRCA2 positive, and the small remainder (2%) had both mutations. Clinical stage proportions were as follows: I (19%), II (63%), and III (18%). Almost three-fourths of patients (70%) had TNBC, and 45% had nodal involvement upon enrollment.

Patients were randomized at a 1:1 ratio to receive either cisplatin (75 mg/m² every 3 weeks for four cycles) or standard AC (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m² every 2-3 weeks for four cycles). These treatments were followed by surgery. The primary endpoint was pCR . Secondary endpoints included residual cancer burden of 0-1 (RCB 0/1), 3-year disease-free survival, and toxicities.

Most patients completed the regimens as planned; however, seven patients received more than four cycles of chemotherapy while four patients completed fewer than four cycles. These 11 patients were categorized as not having a pathologic complete response.

Among the remaining patients, platinum-based chemotherapy was associated with an 18% pCR rate, compared with 26% for standard AC, which translated to a risk ratio of 0.70 that was not significant. Among patients with TNBC (n = 82), pCR rates followed a similar trend (22% vs. 28%), again without statistical significance. For patients with estrogen receptor–positive disease, the numerical disparity in pCR rate was greater (cisplatin at 6% vs. AC at 21%); however, once more, this difference was not statistically significant. Because of the small number of patients in this subgroup (n = 35), Dr. Tung advised that results be interpreted with caution.

Results for RCB 0/1 were similar to pCR. AC was associated with a higher rate of RCB 0-1 for all patients (46% vs. 33%), patients with TNBC (47% vs. 36%), and patients with hormone receptor–positive disease (42% vs. 25%). Across all patients and subtypes, these differences were not statistically significant.

Safety profiles were similar to previously published data for both regimens.

“In conclusion, contrary to our initial expectations, the pCR rate and RCB 0/1 rate is not significantly higher after cisplatin than after AC in BRCA carriers with early-stage breast cancer, whether triple-negative or estrogen receptor–positive HER2-negative disease,” Dr. Tung said. “Our statistician has concluded that there is no realistic scenario by which the pCR with cisplatin would have been significantly higher than with AC had this study met its accrual.”

“We believe the results of the INFORM trial are consistent with those of the GeparSixto and BrightTNess neoadjuvant trials,” Dr. Tung said. “One interpretation of the INFORM trial results, as well as these two trials, is that breast cancer in BRCA carriers is more sensitive than in noncarriers to DNA-damaging agents. … BRCA deficiency or homologous combination deficiency may simply be a marker of sensitivity to DNA-damaging chemotherapy rather than platinum agents specifically.”

The investigators disclosed relationships with Merck, AstraZeneca, Genentech, and others.

SOURCE: Tung N et al. SABCS 2019, Abstract GS6-03.

For third- or fourth-line treatment of metastatic renal cell carcinoma, the vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor tivozanib may offer better progression-free survival than sorafenib, another VEGFR inhibitor, based on results from the TIVO-3 trial.

Susan London/MDedge News

Tivozanib also had fewer dose reductions and dose interruptions than sorafenib, likely because of less off-target activity, reported lead author Brian I. Rini, MD, of the Cleveland Clinic and Case Western Reserve University, also in Cleveland, and colleagues.

“These results support tivozanib as a treatment option for patients with recurrent and progressive renal cell carcinoma, including those who have progressed after previous immunotherapy,” the investigators wrote in Lancet Oncology.

The open-label, phase 3 trial involved 350 patients with metastatic renal cell carcinoma who had been treated with two or more systemic therapies, at least one of which was a VEGFR inhibitor. Patients were randomized in 1:1 ratio to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily on a continuous basis. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, objective response rates, and duration of response. Endpoints were evaluated by independent review. Safety was reported for all patients who received one or more doses of therapy.

After a median follow-up of 19 months, tivozanib was associated with a median progression-free survival of 5.6 months, compared with 3.9 months for sorafenib (P = .016). Significantly more patients in the tivozanib group achieved a response, and at 1 year, 71% of patients in the tivozanib group maintained a response, compared with 46% of the patients in the sorafenib group. At data cutoff, median overall survival was not significantly different between groups.

The most common treatment-related grade 3-4 adverse event was hypertension, which occurred in a slightly higher rate among those treated with tivozanib (20% vs. 14%). Serious treatment-related adverse events occurred at comparable rates in each treatment arm, at 11% for tivozanib and 10% for sorafenib. Compared with patients who received sorafenib, those in the tivozanib group had fewer dose reductions (24% vs. 38%) and dose interruptions (48% vs. 63%) because of adverse events, a benefit that the investigators attributed to relatively lower class-related off-target activity.

“To our knowledge, TIVO-3 provides the largest amount of prospective data generated to date regarding the use of VEGFR tyrosine kinase inhibitors after checkpoint inhibitor treatment,” the investigators wrote. “Notably, the benefit of tivozanib extended to patients who had previously received checkpoint inhibitors and those treated with two previous tyrosine kinase inhibitors.”

The study was funded by AVEO Oncology. The investigators reported additional relationships with Pfizer, Eisai, Astellas, and others.

SOURCE: Rini BI et al. Lancet Oncol. 2019 Dec 3. doi: 10.1016/S1470-2045(19)30735-1.

For third- or fourth-line treatment of metastatic renal cell carcinoma, the vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor tivozanib may offer better progression-free survival than sorafenib, another VEGFR inhibitor, based on results from the TIVO-3 trial.

Susan London/MDedge News

Tivozanib also had fewer dose reductions and dose interruptions than sorafenib, likely because of less off-target activity, reported lead author Brian I. Rini, MD, of the Cleveland Clinic and Case Western Reserve University, also in Cleveland, and colleagues.

“These results support tivozanib as a treatment option for patients with recurrent and progressive renal cell carcinoma, including those who have progressed after previous immunotherapy,” the investigators wrote in Lancet Oncology.

The open-label, phase 3 trial involved 350 patients with metastatic renal cell carcinoma who had been treated with two or more systemic therapies, at least one of which was a VEGFR inhibitor. Patients were randomized in 1:1 ratio to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily on a continuous basis. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, objective response rates, and duration of response. Endpoints were evaluated by independent review. Safety was reported for all patients who received one or more doses of therapy.

After a median follow-up of 19 months, tivozanib was associated with a median progression-free survival of 5.6 months, compared with 3.9 months for sorafenib (P = .016). Significantly more patients in the tivozanib group achieved a response, and at 1 year, 71% of patients in the tivozanib group maintained a response, compared with 46% of the patients in the sorafenib group. At data cutoff, median overall survival was not significantly different between groups.

The most common treatment-related grade 3-4 adverse event was hypertension, which occurred in a slightly higher rate among those treated with tivozanib (20% vs. 14%). Serious treatment-related adverse events occurred at comparable rates in each treatment arm, at 11% for tivozanib and 10% for sorafenib. Compared with patients who received sorafenib, those in the tivozanib group had fewer dose reductions (24% vs. 38%) and dose interruptions (48% vs. 63%) because of adverse events, a benefit that the investigators attributed to relatively lower class-related off-target activity.

“To our knowledge, TIVO-3 provides the largest amount of prospective data generated to date regarding the use of VEGFR tyrosine kinase inhibitors after checkpoint inhibitor treatment,” the investigators wrote. “Notably, the benefit of tivozanib extended to patients who had previously received checkpoint inhibitors and those treated with two previous tyrosine kinase inhibitors.”

The study was funded by AVEO Oncology. The investigators reported additional relationships with Pfizer, Eisai, Astellas, and others.

SOURCE: Rini BI et al. Lancet Oncol. 2019 Dec 3. doi: 10.1016/S1470-2045(19)30735-1.

For third- or fourth-line treatment of metastatic renal cell carcinoma, the vascular epidermal growth factor receptor (VEGFR) tyrosine kinase inhibitor tivozanib may offer better progression-free survival than sorafenib, another VEGFR inhibitor, based on results from the TIVO-3 trial.

Susan London/MDedge News

Tivozanib also had fewer dose reductions and dose interruptions than sorafenib, likely because of less off-target activity, reported lead author Brian I. Rini, MD, of the Cleveland Clinic and Case Western Reserve University, also in Cleveland, and colleagues.

“These results support tivozanib as a treatment option for patients with recurrent and progressive renal cell carcinoma, including those who have progressed after previous immunotherapy,” the investigators wrote in Lancet Oncology.

The open-label, phase 3 trial involved 350 patients with metastatic renal cell carcinoma who had been treated with two or more systemic therapies, at least one of which was a VEGFR inhibitor. Patients were randomized in 1:1 ratio to receive either tivozanib 1.5 mg orally once daily in 4-week cycles or sorafenib 400 mg orally twice daily on a continuous basis. The primary endpoint was progression-free survival. Secondary endpoints included overall survival, objective response rates, and duration of response. Endpoints were evaluated by independent review. Safety was reported for all patients who received one or more doses of therapy.

After a median follow-up of 19 months, tivozanib was associated with a median progression-free survival of 5.6 months, compared with 3.9 months for sorafenib (P = .016). Significantly more patients in the tivozanib group achieved a response, and at 1 year, 71% of patients in the tivozanib group maintained a response, compared with 46% of the patients in the sorafenib group. At data cutoff, median overall survival was not significantly different between groups.

The most common treatment-related grade 3-4 adverse event was hypertension, which occurred in a slightly higher rate among those treated with tivozanib (20% vs. 14%). Serious treatment-related adverse events occurred at comparable rates in each treatment arm, at 11% for tivozanib and 10% for sorafenib. Compared with patients who received sorafenib, those in the tivozanib group had fewer dose reductions (24% vs. 38%) and dose interruptions (48% vs. 63%) because of adverse events, a benefit that the investigators attributed to relatively lower class-related off-target activity.

“To our knowledge, TIVO-3 provides the largest amount of prospective data generated to date regarding the use of VEGFR tyrosine kinase inhibitors after checkpoint inhibitor treatment,” the investigators wrote. “Notably, the benefit of tivozanib extended to patients who had previously received checkpoint inhibitors and those treated with two previous tyrosine kinase inhibitors.”

The study was funded by AVEO Oncology. The investigators reported additional relationships with Pfizer, Eisai, Astellas, and others.

SOURCE: Rini BI et al. Lancet Oncol. 2019 Dec 3. doi: 10.1016/S1470-2045(19)30735-1.

SAN ANTONIO – In the neoadjuvant setting, weekly nab-paclitaxel outmatches a “two-out-of-three” regimen for patients with early-stage triple-negative breast cancer (TNBC), based on results from the phase 3 GeparX trial.

In contrast, neoadjuvant denosumab had no impact on pathologic complete response (pCR), according to lead author Jens-Uwe Blohmer, MD, of Charité University Medical Center in Berlin.

Will Pass/MDedge News

“The anti-cancer activity of RANK-ligand inhibition with denosumab is still under discussion,” Dr. Blohmer said while presenting findings at the San Antonio Breast Cancer Symposium. “The GeparSepto study demonstrated an increased pCR rate with weekly nab-paclitaxel but it remained unclear which schedule should be preferred for nab-paclitaxel in terms of toxicity and efficacy. And that is why the GeparX study addresses both questions in a two-by-two factorial design.”

GeparX involved 780 patients with early breast cancer who were stratified by subtype, stromal tumor-infiltrating lymphocytes (sTILs), and epirubicin/cyclophosphamide (EC) schedule. Following randomization, nab-paclitaxel was delivered at a dose of 125 mg/m² on a weekly basis or on days 1 and 8 on a 22-day cycle (two-out-of-three schedule) for 12 weeks, followed by an additional 12 weeks of EC (90/600 mg/m² every 2 weeks or 3 weeks). Each of these regimens was given with or without denosumab, which when delivered, was given at a dose of 120 mg every 4 weeks throughout the 24-week treatment period. Patients with HER2-positive breast cancer were also given trastuzumab plus pertuzumab, whereas women with TNBC received carboplatin plus taxane-based chemotherapy. All patients underwent surgery after treatment, at which point pCR rate, the primary endpoint, was determined. Of note, the prespecified significance level was higher than typical for oncology trials (alpha = .1).

At baseline, patient characteristics were comparable across the treatment arms. Median age was 49 years; 40% of patients had positive clinical nodal status; 83% of patients had Ki-67 expression greater than 20%; and 8% of patients had sTIL expression greater than 50%. The most common disease subtypes were triple-negative (40.6%) and HER2-positive/HR-positive (39.7%), followed by HER2-positive/HR-negative (19.6%).

Across subtypes, weekly nab-paclitaxel was associated with a significantly higher pCR rate than the two-out-of-three schedule (44.9% vs. 39%; P = .062). Denosumab had no such benefit; pCR rate with denosumab was 41.0%, versus 42.8% without denosumab, a slight difference that lacked statistical significance (P = .582).

A closer look at the nab-paclitaxel subtype data showed that patients with TNBC were deriving significant benefit from the weekly regimen instead of the two-out-of-three schedule (60.4% vs. 50.0%; P = .056), while patients with either of other two subtypes were not.

Although weekly dosing of nab-paclitaxel was superior from the standpoint of pCR, this efficacy advantage came with some trade-offs in tolerability. In the weekly group, 20.6% of patients discontinued nab-paclitaxel, compared with just 6.3% of patients in the two-out-of-three group. Discontinuations were most often due to adverse events, which occurred at a rate of 17.5% in the weekly arm, versus 3.7% among patients given the two-out-of-three regimen. Serious adverse events were also more common in the weekly cohort (31.5% vs. 24.4%).

Concluding his presentation, Dr. Blohmer summarized the key clinical finding.

“In triple-negative breast cancer, optimized neoadjuvant chemotherapy with nab-paclitaxel 125 mg/m² weekly plus carboplatin followed by EC achieves a remarkable pCR rate of at least 60%,” Dr. Blohmer said, adding that further translational research is ongoing.

Following the presentation, perennial symposium fixture Steven Vogl, MD, a practicing oncologist in New York, raised concerns about diminished quality of life that may result from the proposed nab-paclitaxel regimen.

“I really want to know how many patients had prolonged and significant neuropathy after they were finished,” Dr. Vogl said. “In the previous GBG trial, where 125 [mg/m²] of nab-paclitaxel was actually reduced from 150 [mg/m²], some of us thought that was too much neuropathy to give to our patients, because the ones who survived were moderately miserable. Survival and moderately miserable isn’t good enough. How many people had prolonged neuropathy?”

Dr. Blohmer acknowledged this concern.

“It is an excellent question, like I expected,” Dr. Blohmer said. “[Neuropathy] was one of our secondary study endpoints, but we haven’t yet the results. ... We will present our data later, at least, during our full publication.”

The study was funded by Amgen and Celgene. The investigators reported additional relationships with AstraZeneca, Pfizer, Pharma Mar, Daiichi Sankyo, and others.

SOURCE: Blohmer et al. SABCS. 2019 Dec 12. Abstract GS3-01.

SAN ANTONIO – In the neoadjuvant setting, weekly nab-paclitaxel outmatches a “two-out-of-three” regimen for patients with early-stage triple-negative breast cancer (TNBC), based on results from the phase 3 GeparX trial.

In contrast, neoadjuvant denosumab had no impact on pathologic complete response (pCR), according to lead author Jens-Uwe Blohmer, MD, of Charité University Medical Center in Berlin.

Will Pass/MDedge News

“The anti-cancer activity of RANK-ligand inhibition with denosumab is still under discussion,” Dr. Blohmer said while presenting findings at the San Antonio Breast Cancer Symposium. “The GeparSepto study demonstrated an increased pCR rate with weekly nab-paclitaxel but it remained unclear which schedule should be preferred for nab-paclitaxel in terms of toxicity and efficacy. And that is why the GeparX study addresses both questions in a two-by-two factorial design.”

GeparX involved 780 patients with early breast cancer who were stratified by subtype, stromal tumor-infiltrating lymphocytes (sTILs), and epirubicin/cyclophosphamide (EC) schedule. Following randomization, nab-paclitaxel was delivered at a dose of 125 mg/m² on a weekly basis or on days 1 and 8 on a 22-day cycle (two-out-of-three schedule) for 12 weeks, followed by an additional 12 weeks of EC (90/600 mg/m² every 2 weeks or 3 weeks). Each of these regimens was given with or without denosumab, which when delivered, was given at a dose of 120 mg every 4 weeks throughout the 24-week treatment period. Patients with HER2-positive breast cancer were also given trastuzumab plus pertuzumab, whereas women with TNBC received carboplatin plus taxane-based chemotherapy. All patients underwent surgery after treatment, at which point pCR rate, the primary endpoint, was determined. Of note, the prespecified significance level was higher than typical for oncology trials (alpha = .1).

At baseline, patient characteristics were comparable across the treatment arms. Median age was 49 years; 40% of patients had positive clinical nodal status; 83% of patients had Ki-67 expression greater than 20%; and 8% of patients had sTIL expression greater than 50%. The most common disease subtypes were triple-negative (40.6%) and HER2-positive/HR-positive (39.7%), followed by HER2-positive/HR-negative (19.6%).

Across subtypes, weekly nab-paclitaxel was associated with a significantly higher pCR rate than the two-out-of-three schedule (44.9% vs. 39%; P = .062). Denosumab had no such benefit; pCR rate with denosumab was 41.0%, versus 42.8% without denosumab, a slight difference that lacked statistical significance (P = .582).

A closer look at the nab-paclitaxel subtype data showed that patients with TNBC were deriving significant benefit from the weekly regimen instead of the two-out-of-three schedule (60.4% vs. 50.0%; P = .056), while patients with either of other two subtypes were not.

Although weekly dosing of nab-paclitaxel was superior from the standpoint of pCR, this efficacy advantage came with some trade-offs in tolerability. In the weekly group, 20.6% of patients discontinued nab-paclitaxel, compared with just 6.3% of patients in the two-out-of-three group. Discontinuations were most often due to adverse events, which occurred at a rate of 17.5% in the weekly arm, versus 3.7% among patients given the two-out-of-three regimen. Serious adverse events were also more common in the weekly cohort (31.5% vs. 24.4%).

Concluding his presentation, Dr. Blohmer summarized the key clinical finding.

“In triple-negative breast cancer, optimized neoadjuvant chemotherapy with nab-paclitaxel 125 mg/m² weekly plus carboplatin followed by EC achieves a remarkable pCR rate of at least 60%,” Dr. Blohmer said, adding that further translational research is ongoing.

Following the presentation, perennial symposium fixture Steven Vogl, MD, a practicing oncologist in New York, raised concerns about diminished quality of life that may result from the proposed nab-paclitaxel regimen.

“I really want to know how many patients had prolonged and significant neuropathy after they were finished,” Dr. Vogl said. “In the previous GBG trial, where 125 [mg/m²] of nab-paclitaxel was actually reduced from 150 [mg/m²], some of us thought that was too much neuropathy to give to our patients, because the ones who survived were moderately miserable. Survival and moderately miserable isn’t good enough. How many people had prolonged neuropathy?”

Dr. Blohmer acknowledged this concern.

“It is an excellent question, like I expected,” Dr. Blohmer said. “[Neuropathy] was one of our secondary study endpoints, but we haven’t yet the results. ... We will present our data later, at least, during our full publication.”

The study was funded by Amgen and Celgene. The investigators reported additional relationships with AstraZeneca, Pfizer, Pharma Mar, Daiichi Sankyo, and others.

SOURCE: Blohmer et al. SABCS. 2019 Dec 12. Abstract GS3-01.

SAN ANTONIO – In the neoadjuvant setting, weekly nab-paclitaxel outmatches a “two-out-of-three” regimen for patients with early-stage triple-negative breast cancer (TNBC), based on results from the phase 3 GeparX trial.

In contrast, neoadjuvant denosumab had no impact on pathologic complete response (pCR), according to lead author Jens-Uwe Blohmer, MD, of Charité University Medical Center in Berlin.

Will Pass/MDedge News

“The anti-cancer activity of RANK-ligand inhibition with denosumab is still under discussion,” Dr. Blohmer said while presenting findings at the San Antonio Breast Cancer Symposium. “The GeparSepto study demonstrated an increased pCR rate with weekly nab-paclitaxel but it remained unclear which schedule should be preferred for nab-paclitaxel in terms of toxicity and efficacy. And that is why the GeparX study addresses both questions in a two-by-two factorial design.”

GeparX involved 780 patients with early breast cancer who were stratified by subtype, stromal tumor-infiltrating lymphocytes (sTILs), and epirubicin/cyclophosphamide (EC) schedule. Following randomization, nab-paclitaxel was delivered at a dose of 125 mg/m² on a weekly basis or on days 1 and 8 on a 22-day cycle (two-out-of-three schedule) for 12 weeks, followed by an additional 12 weeks of EC (90/600 mg/m² every 2 weeks or 3 weeks). Each of these regimens was given with or without denosumab, which when delivered, was given at a dose of 120 mg every 4 weeks throughout the 24-week treatment period. Patients with HER2-positive breast cancer were also given trastuzumab plus pertuzumab, whereas women with TNBC received carboplatin plus taxane-based chemotherapy. All patients underwent surgery after treatment, at which point pCR rate, the primary endpoint, was determined. Of note, the prespecified significance level was higher than typical for oncology trials (alpha = .1).

At baseline, patient characteristics were comparable across the treatment arms. Median age was 49 years; 40% of patients had positive clinical nodal status; 83% of patients had Ki-67 expression greater than 20%; and 8% of patients had sTIL expression greater than 50%. The most common disease subtypes were triple-negative (40.6%) and HER2-positive/HR-positive (39.7%), followed by HER2-positive/HR-negative (19.6%).

Across subtypes, weekly nab-paclitaxel was associated with a significantly higher pCR rate than the two-out-of-three schedule (44.9% vs. 39%; P = .062). Denosumab had no such benefit; pCR rate with denosumab was 41.0%, versus 42.8% without denosumab, a slight difference that lacked statistical significance (P = .582).

A closer look at the nab-paclitaxel subtype data showed that patients with TNBC were deriving significant benefit from the weekly regimen instead of the two-out-of-three schedule (60.4% vs. 50.0%; P = .056), while patients with either of other two subtypes were not.

Although weekly dosing of nab-paclitaxel was superior from the standpoint of pCR, this efficacy advantage came with some trade-offs in tolerability. In the weekly group, 20.6% of patients discontinued nab-paclitaxel, compared with just 6.3% of patients in the two-out-of-three group. Discontinuations were most often due to adverse events, which occurred at a rate of 17.5% in the weekly arm, versus 3.7% among patients given the two-out-of-three regimen. Serious adverse events were also more common in the weekly cohort (31.5% vs. 24.4%).

Concluding his presentation, Dr. Blohmer summarized the key clinical finding.

“In triple-negative breast cancer, optimized neoadjuvant chemotherapy with nab-paclitaxel 125 mg/m² weekly plus carboplatin followed by EC achieves a remarkable pCR rate of at least 60%,” Dr. Blohmer said, adding that further translational research is ongoing.

Following the presentation, perennial symposium fixture Steven Vogl, MD, a practicing oncologist in New York, raised concerns about diminished quality of life that may result from the proposed nab-paclitaxel regimen.

“I really want to know how many patients had prolonged and significant neuropathy after they were finished,” Dr. Vogl said. “In the previous GBG trial, where 125 [mg/m²] of nab-paclitaxel was actually reduced from 150 [mg/m²], some of us thought that was too much neuropathy to give to our patients, because the ones who survived were moderately miserable. Survival and moderately miserable isn’t good enough. How many people had prolonged neuropathy?”

Dr. Blohmer acknowledged this concern.

“It is an excellent question, like I expected,” Dr. Blohmer said. “[Neuropathy] was one of our secondary study endpoints, but we haven’t yet the results. ... We will present our data later, at least, during our full publication.”

The study was funded by Amgen and Celgene. The investigators reported additional relationships with AstraZeneca, Pfizer, Pharma Mar, Daiichi Sankyo, and others.

SOURCE: Blohmer et al. SABCS. 2019 Dec 12. Abstract GS3-01.

SAN ANTONIO – Residual cancer burden (RCB) is poised to alter American Joint Committee on Cancer (AJCC) staging standards in breast cancer, according to investigators.

Will Pass/MDedge News

A meta-analysis showed that RCB – which is calculated in the neoadjuvant setting through a combination of primary tumor bed cellularity, lymph node positivity, and size of largest metastasis – was significantly associated with long-term survival of more than 5,000 breast cancer patients, reported principal investigator W. Fraser Symmans, MD, of MD Anderson Cancer Center, Houston, who presented the findings at the San Antonio Breast Cancer Symposium.

Will Pass/MDedge News

Coinvestigator Laura J. Esserman, MD, of the University of California, San Francisco, who was in attendance at Dr. Symmans’ presentation, put the study in context.

“The reason we did this meta-analysis was to really change the joint commission – the AJCC staging – and we expect that will happen on the basis of these results,” Dr. Esserman said. “[RBC] is, moving forward, the standard of care.”

The investigators analyzed individual-level data from 5,160 patients treated at multiple institutions. For each patient, RCB, which is scored from 0 to III, from pathologic complete response (0) to high disease burden (III), was compared with event-free survival (EFS) and disease relapse-free survival (DRFS).

Will Pass/MDedge News

“I ask my pathologist to give me the RCB score,” Dr. Kaklamani said. “The question is, what do I do with the results? It’s a little limited. In triple-negative patients I may consider giving capecitabine in the adjuvant setting, or obviously enrolling them in clinical trials. In my HER2-positive patients, I will look at the results from the KATHERINE trial and the ExteNET trial to guide me. In my HR-positive patients, I’m still waiting for results from other trials to see how these results can be interpreted. What we’ve [found] is in many trials, achieving a pathologic complete response in HR-positive patients may not be as important, but as you can see here, it looks like RCB really is.”

The investigators disclosed relationships with Seattle Genetics, Almac, Syndax, and others.
 

SOURCE: Yau et al. SABCS. 2019 Dec 13. Abstract GS5-01.

SAN ANTONIO – Residual cancer burden (RCB) is poised to alter American Joint Committee on Cancer (AJCC) staging standards in breast cancer, according to investigators.

Will Pass/MDedge News

A meta-analysis showed that RCB – which is calculated in the neoadjuvant setting through a combination of primary tumor bed cellularity, lymph node positivity, and size of largest metastasis – was significantly associated with long-term survival of more than 5,000 breast cancer patients, reported principal investigator W. Fraser Symmans, MD, of MD Anderson Cancer Center, Houston, who presented the findings at the San Antonio Breast Cancer Symposium.

Will Pass/MDedge News

Coinvestigator Laura J. Esserman, MD, of the University of California, San Francisco, who was in attendance at Dr. Symmans’ presentation, put the study in context.

“The reason we did this meta-analysis was to really change the joint commission – the AJCC staging – and we expect that will happen on the basis of these results,” Dr. Esserman said. “[RBC] is, moving forward, the standard of care.”

The investigators analyzed individual-level data from 5,160 patients treated at multiple institutions. For each patient, RCB, which is scored from 0 to III, from pathologic complete response (0) to high disease burden (III), was compared with event-free survival (EFS) and disease relapse-free survival (DRFS).

Will Pass/MDedge News

“I ask my pathologist to give me the RCB score,” Dr. Kaklamani said. “The question is, what do I do with the results? It’s a little limited. In triple-negative patients I may consider giving capecitabine in the adjuvant setting, or obviously enrolling them in clinical trials. In my HER2-positive patients, I will look at the results from the KATHERINE trial and the ExteNET trial to guide me. In my HR-positive patients, I’m still waiting for results from other trials to see how these results can be interpreted. What we’ve [found] is in many trials, achieving a pathologic complete response in HR-positive patients may not be as important, but as you can see here, it looks like RCB really is.”

The investigators disclosed relationships with Seattle Genetics, Almac, Syndax, and others.
 

SOURCE: Yau et al. SABCS. 2019 Dec 13. Abstract GS5-01.

SAN ANTONIO – Residual cancer burden (RCB) is poised to alter American Joint Committee on Cancer (AJCC) staging standards in breast cancer, according to investigators.

Will Pass/MDedge News

A meta-analysis showed that RCB – which is calculated in the neoadjuvant setting through a combination of primary tumor bed cellularity, lymph node positivity, and size of largest metastasis – was significantly associated with long-term survival of more than 5,000 breast cancer patients, reported principal investigator W. Fraser Symmans, MD, of MD Anderson Cancer Center, Houston, who presented the findings at the San Antonio Breast Cancer Symposium.

Will Pass/MDedge News

Coinvestigator Laura J. Esserman, MD, of the University of California, San Francisco, who was in attendance at Dr. Symmans’ presentation, put the study in context.

“The reason we did this meta-analysis was to really change the joint commission – the AJCC staging – and we expect that will happen on the basis of these results,” Dr. Esserman said. “[RBC] is, moving forward, the standard of care.”

The investigators analyzed individual-level data from 5,160 patients treated at multiple institutions. For each patient, RCB, which is scored from 0 to III, from pathologic complete response (0) to high disease burden (III), was compared with event-free survival (EFS) and disease relapse-free survival (DRFS).

Will Pass/MDedge News

“I ask my pathologist to give me the RCB score,” Dr. Kaklamani said. “The question is, what do I do with the results? It’s a little limited. In triple-negative patients I may consider giving capecitabine in the adjuvant setting, or obviously enrolling them in clinical trials. In my HER2-positive patients, I will look at the results from the KATHERINE trial and the ExteNET trial to guide me. In my HR-positive patients, I’m still waiting for results from other trials to see how these results can be interpreted. What we’ve [found] is in many trials, achieving a pathologic complete response in HR-positive patients may not be as important, but as you can see here, it looks like RCB really is.”

The investigators disclosed relationships with Seattle Genetics, Almac, Syndax, and others.
 

SOURCE: Yau et al. SABCS. 2019 Dec 13. Abstract GS5-01.

A new risk prediction panel based on machine learning may enable routine, noninvasive identification of patients with a high risk of Barrett’s esophagus, according to investigators.

The methods used in the present study could potentially be applied to other conditions to aid in diagnosis and limit low-yield invasive testing, reported lead author Avi Rosenfeld, PhD, of Jerusalem College of Technology in Israel, and colleagues.

“The currently used system for identifying patients with Barrett’s esophagus, or those at risk of esophageal adenocarcinoma, is flawed because it is based on symptoms that trigger expensive and unpleasant invasive tests,” the investigators wrote. Their report is in The Lancet Digital Health.

In an effort to improve early clinical clarity, the investigators turned to machine learning. Algorithm development and testing relied upon data from more than 1,600 patients involved in two case-control trials, BEST2 and BOOST. From BEST2, 1,299 patients were randomized in a 6:4 ratio to generate a training dataset (n = 776) and a testing dataset (n = 523). Data from all 398 patients in the BOOST trial were used for external validation. Barrett’s esophagus was common in both trials, with a prevalence of 68% and 50% in BEST2 and BOOST, respectively.

During the training phase, machine learning identified independent patient characteristics associated with a diagnosis of Barrett’s esophagus. Specific artificial intelligence techniques included information gain and correlation-based feature selection.

“Both information gain and correlation-based feature selection are filter feature selection methods and thus have the advantage of being fast, scalable, and independent of the classifier,” the investigators noted. They explained that independence from the classifier is “crucial,” as this characteristic has been associated with improved interpretability and more stable algorithms than conventional statistical approaches.

The training process revealed eight distinct diagnostic features: sex, age, waist circumference, cigarette smoking, duration of acidic taste, duration of heartburn, frequency of stomach pain, and use of antireflux medication. All of these were directly correlated with Barrett’s esophagus, except for frequency of stomach pain, which had an inverse relationship. The investigators noted that this inverse relationship may initially seem counterintuitive, but a closer look suggests that the relationship is appropriate.

“Most patients with esophageal adenocarcinoma are not identified before cancer develops despite many of them having Barrett’s esophagus,” the investigators wrote. “Indeed, 40% of patients with esophageal adenocarcinoma have not previously had symptomatic reflux and many probably had Barrett’s esophagus. Therefore, Barrett’s esophagus has been hypothesized to not be associated with severity of reflux symptoms; which fits with the model determined from our data.”

To provide a test of the model’s predictive ability, the investigators arbitrarily set sensitivity at 90%. Within this context, logistic regression was used to provide an upper estimate of the model’s predictive ability; this resulted in an area under the receiver-operator curve (AUC) of 0.87 and a specificity of 68%. In the validation phase, these figures decreased slightly. In the testing dataset, AUC was 0.86, while specificity was 65%. External validation was associated with an AUC of 0.81 and a specificity of 58%.

“We have shown that a panel with eight features, including detailed stomach and chest symptoms, can identify the presence of Barrett’s esophagus with high sensitivity and specificity in a case-control population,” the investigators concluded.

“Simple triaging of individuals might be possible on the basis of predictive panels that include variables that are widely available or easy to obtain,” they added. “Patient age and sex, together with medication and smoking history, are routinely captured in primary care systems. Additionally, asking about duration of heartburn and acidic taste, frequency of stomach pain, and measuring waist circumference should be simple for physicians. Alternatively, a patient could do a self-assessment using a web-based app and generate a personalized risk profile for having Barrett’s esophagus.”

The study was funded by the Charles Wolfson Charitable Trust and Guts UK, the National Institute for Health Research Biomedical Research Centre, Cancer Research UK, and the Wellcome/EPSRC Centre for Interventional and Surgical Sciences at University College London. Dr. Fitzgerald reported a relationship with Medtronic via licensing of the cytosponge device.

SOURCE: Rosenfeld A et al. Lancet Digital Health. 2019 Dec 5. doi: 10.1016/S2589-7500(19)30216-X.

A new risk prediction panel based on machine learning may enable routine, noninvasive identification of patients with a high risk of Barrett’s esophagus, according to investigators.

The methods used in the present study could potentially be applied to other conditions to aid in diagnosis and limit low-yield invasive testing, reported lead author Avi Rosenfeld, PhD, of Jerusalem College of Technology in Israel, and colleagues.

“The currently used system for identifying patients with Barrett’s esophagus, or those at risk of esophageal adenocarcinoma, is flawed because it is based on symptoms that trigger expensive and unpleasant invasive tests,” the investigators wrote. Their report is in The Lancet Digital Health.

In an effort to improve early clinical clarity, the investigators turned to machine learning. Algorithm development and testing relied upon data from more than 1,600 patients involved in two case-control trials, BEST2 and BOOST. From BEST2, 1,299 patients were randomized in a 6:4 ratio to generate a training dataset (n = 776) and a testing dataset (n = 523). Data from all 398 patients in the BOOST trial were used for external validation. Barrett’s esophagus was common in both trials, with a prevalence of 68% and 50% in BEST2 and BOOST, respectively.

During the training phase, machine learning identified independent patient characteristics associated with a diagnosis of Barrett’s esophagus. Specific artificial intelligence techniques included information gain and correlation-based feature selection.

“Both information gain and correlation-based feature selection are filter feature selection methods and thus have the advantage of being fast, scalable, and independent of the classifier,” the investigators noted. They explained that independence from the classifier is “crucial,” as this characteristic has been associated with improved interpretability and more stable algorithms than conventional statistical approaches.

The training process revealed eight distinct diagnostic features: sex, age, waist circumference, cigarette smoking, duration of acidic taste, duration of heartburn, frequency of stomach pain, and use of antireflux medication. All of these were directly correlated with Barrett’s esophagus, except for frequency of stomach pain, which had an inverse relationship. The investigators noted that this inverse relationship may initially seem counterintuitive, but a closer look suggests that the relationship is appropriate.

“Most patients with esophageal adenocarcinoma are not identified before cancer develops despite many of them having Barrett’s esophagus,” the investigators wrote. “Indeed, 40% of patients with esophageal adenocarcinoma have not previously had symptomatic reflux and many probably had Barrett’s esophagus. Therefore, Barrett’s esophagus has been hypothesized to not be associated with severity of reflux symptoms; which fits with the model determined from our data.”

To provide a test of the model’s predictive ability, the investigators arbitrarily set sensitivity at 90%. Within this context, logistic regression was used to provide an upper estimate of the model’s predictive ability; this resulted in an area under the receiver-operator curve (AUC) of 0.87 and a specificity of 68%. In the validation phase, these figures decreased slightly. In the testing dataset, AUC was 0.86, while specificity was 65%. External validation was associated with an AUC of 0.81 and a specificity of 58%.

“We have shown that a panel with eight features, including detailed stomach and chest symptoms, can identify the presence of Barrett’s esophagus with high sensitivity and specificity in a case-control population,” the investigators concluded.

“Simple triaging of individuals might be possible on the basis of predictive panels that include variables that are widely available or easy to obtain,” they added. “Patient age and sex, together with medication and smoking history, are routinely captured in primary care systems. Additionally, asking about duration of heartburn and acidic taste, frequency of stomach pain, and measuring waist circumference should be simple for physicians. Alternatively, a patient could do a self-assessment using a web-based app and generate a personalized risk profile for having Barrett’s esophagus.”

The study was funded by the Charles Wolfson Charitable Trust and Guts UK, the National Institute for Health Research Biomedical Research Centre, Cancer Research UK, and the Wellcome/EPSRC Centre for Interventional and Surgical Sciences at University College London. Dr. Fitzgerald reported a relationship with Medtronic via licensing of the cytosponge device.

SOURCE: Rosenfeld A et al. Lancet Digital Health. 2019 Dec 5. doi: 10.1016/S2589-7500(19)30216-X.

A new risk prediction panel based on machine learning may enable routine, noninvasive identification of patients with a high risk of Barrett’s esophagus, according to investigators.

The methods used in the present study could potentially be applied to other conditions to aid in diagnosis and limit low-yield invasive testing, reported lead author Avi Rosenfeld, PhD, of Jerusalem College of Technology in Israel, and colleagues.

“The currently used system for identifying patients with Barrett’s esophagus, or those at risk of esophageal adenocarcinoma, is flawed because it is based on symptoms that trigger expensive and unpleasant invasive tests,” the investigators wrote. Their report is in The Lancet Digital Health.

In an effort to improve early clinical clarity, the investigators turned to machine learning. Algorithm development and testing relied upon data from more than 1,600 patients involved in two case-control trials, BEST2 and BOOST. From BEST2, 1,299 patients were randomized in a 6:4 ratio to generate a training dataset (n = 776) and a testing dataset (n = 523). Data from all 398 patients in the BOOST trial were used for external validation. Barrett’s esophagus was common in both trials, with a prevalence of 68% and 50% in BEST2 and BOOST, respectively.

During the training phase, machine learning identified independent patient characteristics associated with a diagnosis of Barrett’s esophagus. Specific artificial intelligence techniques included information gain and correlation-based feature selection.

“Both information gain and correlation-based feature selection are filter feature selection methods and thus have the advantage of being fast, scalable, and independent of the classifier,” the investigators noted. They explained that independence from the classifier is “crucial,” as this characteristic has been associated with improved interpretability and more stable algorithms than conventional statistical approaches.

The training process revealed eight distinct diagnostic features: sex, age, waist circumference, cigarette smoking, duration of acidic taste, duration of heartburn, frequency of stomach pain, and use of antireflux medication. All of these were directly correlated with Barrett’s esophagus, except for frequency of stomach pain, which had an inverse relationship. The investigators noted that this inverse relationship may initially seem counterintuitive, but a closer look suggests that the relationship is appropriate.

“Most patients with esophageal adenocarcinoma are not identified before cancer develops despite many of them having Barrett’s esophagus,” the investigators wrote. “Indeed, 40% of patients with esophageal adenocarcinoma have not previously had symptomatic reflux and many probably had Barrett’s esophagus. Therefore, Barrett’s esophagus has been hypothesized to not be associated with severity of reflux symptoms; which fits with the model determined from our data.”

To provide a test of the model’s predictive ability, the investigators arbitrarily set sensitivity at 90%. Within this context, logistic regression was used to provide an upper estimate of the model’s predictive ability; this resulted in an area under the receiver-operator curve (AUC) of 0.87 and a specificity of 68%. In the validation phase, these figures decreased slightly. In the testing dataset, AUC was 0.86, while specificity was 65%. External validation was associated with an AUC of 0.81 and a specificity of 58%.

“We have shown that a panel with eight features, including detailed stomach and chest symptoms, can identify the presence of Barrett’s esophagus with high sensitivity and specificity in a case-control population,” the investigators concluded.

“Simple triaging of individuals might be possible on the basis of predictive panels that include variables that are widely available or easy to obtain,” they added. “Patient age and sex, together with medication and smoking history, are routinely captured in primary care systems. Additionally, asking about duration of heartburn and acidic taste, frequency of stomach pain, and measuring waist circumference should be simple for physicians. Alternatively, a patient could do a self-assessment using a web-based app and generate a personalized risk profile for having Barrett’s esophagus.”

The study was funded by the Charles Wolfson Charitable Trust and Guts UK, the National Institute for Health Research Biomedical Research Centre, Cancer Research UK, and the Wellcome/EPSRC Centre for Interventional and Surgical Sciences at University College London. Dr. Fitzgerald reported a relationship with Medtronic via licensing of the cytosponge device.

SOURCE: Rosenfeld A et al. Lancet Digital Health. 2019 Dec 5. doi: 10.1016/S2589-7500(19)30216-X.

SAN ANTONIO – For patients with early triple-negative breast cancer (TNBC), adding capecitabine to standard adjuvant chemotherapy may extend disease-free survival (DFS), based results of a phase 3 trial conducted in China.

Will Pass/MDedge News

Although capecitabine boosted DFS by approximately 6%, overall survival remained unchanged, reported lead author Junjie Li, MD, of Fudan University in Shanghai, China.

In a presentation at the San Antonio Breast Cancer Symposium, Dr. Li explained that these findings provide much-needed support for the concomitant use of capecitabine in breast cancer.

“Capecitabine has been proven [effective] in advanced breast cancer, while in earlier stage disease, available data are still inconsistent,” Dr. Li said.

To help resolve some of this uncertainty, Dr. Li and colleagues conducted an open-label, phase 3 trial involving 585 patients with TNBC who were either node positive or negative and had tumors more than 1 cm in diameter. Patients were randomized in a 1:1 ratio to receive either standard therapy with three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil; or three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine.

After a median follow-up of 67 months, 288 patients had received the capecitabine regimen and 273 had undergone standard therapy. The 5-year DFS was significantly longer in the capecitabine group, at 86.26%, than the control group, at 80.23% (hazard ratio, 0.66; P = .038). This benefit extended across subgroups, Dr. Li noted. While a slight numerical difference in overall survival was seen between capecitabine and control arms, this was not statistically significant (93.27% vs. 90.55%).

The investigators described safety profiles between treatment arms as “generally comparable.” In the capecitabine group, more than one-third of patients (38.89%) had dose reductions, while 8.42% reported grade 3-4 hand-foot syndrome. Grade 3-4 toxicities were more common in the capecitabine group, including neutropenia (45.79% vs. 41.32%) and febrile neutropenia (16.5% vs. 15.97%).

“Capecitabine concomitant use with docetaxel and epirubicin may significantly improve disease-free survival in early triple-negative patients,” Dr. Li concluded. He suggested that the study regimen be viewed as an alternative adjuvant regimen, as it provided clinically meaningful improvements in survival while maintaining tolerability.

Conference attendee Mohamed El-Naghy, MD, PhD, a practicing oncologist in Oneida, N.Y., expressed concern for one aspect of the trial methodology during the question and answer session following Dr. Li’s presentation: Although all patients in the trial were considered triple negative, 10 patients had estrogen receptor/progesterone receptor (ER/PR) expression ranging from 1 to 9%, which conflicts with the definition of TNBCr provided by current guidelines, according to Dr. Li.

“It is always important to have common language,” Dr. El-Naghy said. “And if you define [TNBC by] ER/PR negativity, and still you have 10% [expression], that is unacceptable. The whole point is, I looked at your numbers – 10 patients in the whole study – maybe you say they are triple negative, but these [patients] are contamination to your sample.”

Responding to this comment, Dr. Li said that the data from these patients had a minimal impact on the study results.

“We did another analysis to exclude these 10 patients, but still the result is quite similar, because they are just 10 patients – 5 in each group,” Dr. Li said.

Will Pass/MDedge News

Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center, Kansas City, offered some additional viewpoints on the trial.

“A large proportion of patients had non–grade III disease, and one could say that the dose of docetaxel monotherapy in the control arm was not the traditional 100 mg/m², and that could have negatively impacted the outcomes in the control arm,” Dr. Sharma said. “In addition, the trial is representative of patients only from China, and whether these findings would hold true in other ethnic and racial groups is not known. Furthermore, there seemed to be limited efficacy in patients with N0 disease, which comprised two-thirds of the trial.”

Despite these potential limitations, based on the trial results and other evidence, Dr. Sharma suggested that adding capecitabine to standard systemic therapy may be considered a viable option for patients with early TNBC.

The investigators reported no disclosures.

SOURCE: Li J et al. SABCS 2019, Abstract GS1-08.

SAN ANTONIO – For patients with early triple-negative breast cancer (TNBC), adding capecitabine to standard adjuvant chemotherapy may extend disease-free survival (DFS), based results of a phase 3 trial conducted in China.

Will Pass/MDedge News

Although capecitabine boosted DFS by approximately 6%, overall survival remained unchanged, reported lead author Junjie Li, MD, of Fudan University in Shanghai, China.

In a presentation at the San Antonio Breast Cancer Symposium, Dr. Li explained that these findings provide much-needed support for the concomitant use of capecitabine in breast cancer.

“Capecitabine has been proven [effective] in advanced breast cancer, while in earlier stage disease, available data are still inconsistent,” Dr. Li said.

To help resolve some of this uncertainty, Dr. Li and colleagues conducted an open-label, phase 3 trial involving 585 patients with TNBC who were either node positive or negative and had tumors more than 1 cm in diameter. Patients were randomized in a 1:1 ratio to receive either standard therapy with three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil; or three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine.

After a median follow-up of 67 months, 288 patients had received the capecitabine regimen and 273 had undergone standard therapy. The 5-year DFS was significantly longer in the capecitabine group, at 86.26%, than the control group, at 80.23% (hazard ratio, 0.66; P = .038). This benefit extended across subgroups, Dr. Li noted. While a slight numerical difference in overall survival was seen between capecitabine and control arms, this was not statistically significant (93.27% vs. 90.55%).

The investigators described safety profiles between treatment arms as “generally comparable.” In the capecitabine group, more than one-third of patients (38.89%) had dose reductions, while 8.42% reported grade 3-4 hand-foot syndrome. Grade 3-4 toxicities were more common in the capecitabine group, including neutropenia (45.79% vs. 41.32%) and febrile neutropenia (16.5% vs. 15.97%).

“Capecitabine concomitant use with docetaxel and epirubicin may significantly improve disease-free survival in early triple-negative patients,” Dr. Li concluded. He suggested that the study regimen be viewed as an alternative adjuvant regimen, as it provided clinically meaningful improvements in survival while maintaining tolerability.

Conference attendee Mohamed El-Naghy, MD, PhD, a practicing oncologist in Oneida, N.Y., expressed concern for one aspect of the trial methodology during the question and answer session following Dr. Li’s presentation: Although all patients in the trial were considered triple negative, 10 patients had estrogen receptor/progesterone receptor (ER/PR) expression ranging from 1 to 9%, which conflicts with the definition of TNBCr provided by current guidelines, according to Dr. Li.

“It is always important to have common language,” Dr. El-Naghy said. “And if you define [TNBC by] ER/PR negativity, and still you have 10% [expression], that is unacceptable. The whole point is, I looked at your numbers – 10 patients in the whole study – maybe you say they are triple negative, but these [patients] are contamination to your sample.”

Responding to this comment, Dr. Li said that the data from these patients had a minimal impact on the study results.

“We did another analysis to exclude these 10 patients, but still the result is quite similar, because they are just 10 patients – 5 in each group,” Dr. Li said.

Will Pass/MDedge News

Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center, Kansas City, offered some additional viewpoints on the trial.

“A large proportion of patients had non–grade III disease, and one could say that the dose of docetaxel monotherapy in the control arm was not the traditional 100 mg/m², and that could have negatively impacted the outcomes in the control arm,” Dr. Sharma said. “In addition, the trial is representative of patients only from China, and whether these findings would hold true in other ethnic and racial groups is not known. Furthermore, there seemed to be limited efficacy in patients with N0 disease, which comprised two-thirds of the trial.”

Despite these potential limitations, based on the trial results and other evidence, Dr. Sharma suggested that adding capecitabine to standard systemic therapy may be considered a viable option for patients with early TNBC.

The investigators reported no disclosures.

SOURCE: Li J et al. SABCS 2019, Abstract GS1-08.

SAN ANTONIO – For patients with early triple-negative breast cancer (TNBC), adding capecitabine to standard adjuvant chemotherapy may extend disease-free survival (DFS), based results of a phase 3 trial conducted in China.

Will Pass/MDedge News

Although capecitabine boosted DFS by approximately 6%, overall survival remained unchanged, reported lead author Junjie Li, MD, of Fudan University in Shanghai, China.

In a presentation at the San Antonio Breast Cancer Symposium, Dr. Li explained that these findings provide much-needed support for the concomitant use of capecitabine in breast cancer.

“Capecitabine has been proven [effective] in advanced breast cancer, while in earlier stage disease, available data are still inconsistent,” Dr. Li said.

To help resolve some of this uncertainty, Dr. Li and colleagues conducted an open-label, phase 3 trial involving 585 patients with TNBC who were either node positive or negative and had tumors more than 1 cm in diameter. Patients were randomized in a 1:1 ratio to receive either standard therapy with three cycles of docetaxel followed by three cycles of cyclophosphamide, epirubicin, and fluorouracil; or three cycles of capecitabine and docetaxel followed by three cycles of cyclophosphamide, epirubicin, and capecitabine.

After a median follow-up of 67 months, 288 patients had received the capecitabine regimen and 273 had undergone standard therapy. The 5-year DFS was significantly longer in the capecitabine group, at 86.26%, than the control group, at 80.23% (hazard ratio, 0.66; P = .038). This benefit extended across subgroups, Dr. Li noted. While a slight numerical difference in overall survival was seen between capecitabine and control arms, this was not statistically significant (93.27% vs. 90.55%).

The investigators described safety profiles between treatment arms as “generally comparable.” In the capecitabine group, more than one-third of patients (38.89%) had dose reductions, while 8.42% reported grade 3-4 hand-foot syndrome. Grade 3-4 toxicities were more common in the capecitabine group, including neutropenia (45.79% vs. 41.32%) and febrile neutropenia (16.5% vs. 15.97%).

“Capecitabine concomitant use with docetaxel and epirubicin may significantly improve disease-free survival in early triple-negative patients,” Dr. Li concluded. He suggested that the study regimen be viewed as an alternative adjuvant regimen, as it provided clinically meaningful improvements in survival while maintaining tolerability.

Conference attendee Mohamed El-Naghy, MD, PhD, a practicing oncologist in Oneida, N.Y., expressed concern for one aspect of the trial methodology during the question and answer session following Dr. Li’s presentation: Although all patients in the trial were considered triple negative, 10 patients had estrogen receptor/progesterone receptor (ER/PR) expression ranging from 1 to 9%, which conflicts with the definition of TNBCr provided by current guidelines, according to Dr. Li.

“It is always important to have common language,” Dr. El-Naghy said. “And if you define [TNBC by] ER/PR negativity, and still you have 10% [expression], that is unacceptable. The whole point is, I looked at your numbers – 10 patients in the whole study – maybe you say they are triple negative, but these [patients] are contamination to your sample.”

Responding to this comment, Dr. Li said that the data from these patients had a minimal impact on the study results.

“We did another analysis to exclude these 10 patients, but still the result is quite similar, because they are just 10 patients – 5 in each group,” Dr. Li said.

Will Pass/MDedge News

Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center, Kansas City, offered some additional viewpoints on the trial.

“A large proportion of patients had non–grade III disease, and one could say that the dose of docetaxel monotherapy in the control arm was not the traditional 100 mg/m², and that could have negatively impacted the outcomes in the control arm,” Dr. Sharma said. “In addition, the trial is representative of patients only from China, and whether these findings would hold true in other ethnic and racial groups is not known. Furthermore, there seemed to be limited efficacy in patients with N0 disease, which comprised two-thirds of the trial.”

Despite these potential limitations, based on the trial results and other evidence, Dr. Sharma suggested that adding capecitabine to standard systemic therapy may be considered a viable option for patients with early TNBC.

The investigators reported no disclosures.

SOURCE: Li J et al. SABCS 2019, Abstract GS1-08.

SAN ANTONIO – For patients with early, low-risk breast cancer, accelerated partial breast irradiation (APBI) may be considered a standard alternative to whole breast irradiation, according to investigators.

Will Pass/MDedge News

This conclusion was based on 10-year follow-up results from the APBI IMRT Florence phase III trial, which showed that APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation without increasing risks of tumor recurrence or mortality, reported lead author Irco Meattini, MD, of the University of Florence, Italy, and colleagues.

“As we well know, recent developments in radiation oncology ... show a move toward a deescalation strategy for early breast cancer, including accelerated and nonaccelerated partial breast irradiation,” Dr. Meattini said during a presentation at the San Antonio Breast Cancer Symposium. “What we have learned from [previous] phase 3 trials [is that with adequate patient selection for] partial breast irradiation, safety profile and cosmetic outcome are strongly associated with technique – the approach, the dose, the number of fractions per day, and the total dose.”

The current phase 3 trial, which enrolled 520 patients with early breast cancer, aimed to determine long-term efficacy, safety, and cosmetic outcomes for partial versus whole breast irradiation. All patients enrolled were at least 40 years of age and had a maximum pathological tumor size of 25 mm. Patients were randomized in a 1:1 ratio to receive either whole breast irradiation (WBI) at a dose of 50 Gy in 25 fractions, followed by 10 Gy in five fractions delivered to the tumor bed; or APBI, which was delivered to the tumor bed at a dose of 30 Gy in five daily fractions.

The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were overall survival, breast cancer–specific survival, distant metastasis-free survival, locoregional recurrences, and contralateral breast cancer. Adverse events and cosmesis also were evaluated.

Five-year results, previously reported, revealed no significant difference in survival rates or IBTR between treatment techniques, and results of the present 10-year analysis maintained these findings. Between groups, no significant differences were observed in any of the primary or secondary endpoints, suggesting that major efficacy outcomes were unaffected by type of irradiation delivered.

While major efficacy endpoints were comparable between groups, safety profiles and cosmetic results differed significantly.

Adverse events of all levels of severity were significantly more common with WBI than APBI. Grade 2 or higher acute adverse events occurred in 37.7% of patients treated with WBI, compared with just 2.0% of patients treated with APBI (P = .0001). The rate of grade 2 or higher adverse events was also significantly higher in the WBI group than in the APBI group in the late setting, albeit with a narrower margin than in the acute setting (2.7% vs 0%; P = .015). Skin toxicity rates followed a similar pattern, favoring APBI both in the acute phase (66.5% vs. 21.1%; P = .0001) and the late phase (30.0% vs. 4.5%; P = .0001).

In further support of APBI, cosmetic results, as measured by the Harvard Breast Cosmesis Scale, were significantly better in the APBI group than in the WBI group. Both physicians and patients were significantly more likely to report good or excellent cosmetic results with APBI than WBI.

“APBI might be considered a standard alternative to WBI in low risk and very low risk early breast cancer patients,” Dr. Meattini concluded.

The investigators reported no disclosures.

SOURCE: Meattini et al. SABCS. 2019 Dec 12. Abstract GS4-06.

SAN ANTONIO – For patients with early, low-risk breast cancer, accelerated partial breast irradiation (APBI) may be considered a standard alternative to whole breast irradiation, according to investigators.

Will Pass/MDedge News

This conclusion was based on 10-year follow-up results from the APBI IMRT Florence phase III trial, which showed that APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation without increasing risks of tumor recurrence or mortality, reported lead author Irco Meattini, MD, of the University of Florence, Italy, and colleagues.

“As we well know, recent developments in radiation oncology ... show a move toward a deescalation strategy for early breast cancer, including accelerated and nonaccelerated partial breast irradiation,” Dr. Meattini said during a presentation at the San Antonio Breast Cancer Symposium. “What we have learned from [previous] phase 3 trials [is that with adequate patient selection for] partial breast irradiation, safety profile and cosmetic outcome are strongly associated with technique – the approach, the dose, the number of fractions per day, and the total dose.”

The current phase 3 trial, which enrolled 520 patients with early breast cancer, aimed to determine long-term efficacy, safety, and cosmetic outcomes for partial versus whole breast irradiation. All patients enrolled were at least 40 years of age and had a maximum pathological tumor size of 25 mm. Patients were randomized in a 1:1 ratio to receive either whole breast irradiation (WBI) at a dose of 50 Gy in 25 fractions, followed by 10 Gy in five fractions delivered to the tumor bed; or APBI, which was delivered to the tumor bed at a dose of 30 Gy in five daily fractions.

The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were overall survival, breast cancer–specific survival, distant metastasis-free survival, locoregional recurrences, and contralateral breast cancer. Adverse events and cosmesis also were evaluated.

Five-year results, previously reported, revealed no significant difference in survival rates or IBTR between treatment techniques, and results of the present 10-year analysis maintained these findings. Between groups, no significant differences were observed in any of the primary or secondary endpoints, suggesting that major efficacy outcomes were unaffected by type of irradiation delivered.

While major efficacy endpoints were comparable between groups, safety profiles and cosmetic results differed significantly.

Adverse events of all levels of severity were significantly more common with WBI than APBI. Grade 2 or higher acute adverse events occurred in 37.7% of patients treated with WBI, compared with just 2.0% of patients treated with APBI (P = .0001). The rate of grade 2 or higher adverse events was also significantly higher in the WBI group than in the APBI group in the late setting, albeit with a narrower margin than in the acute setting (2.7% vs 0%; P = .015). Skin toxicity rates followed a similar pattern, favoring APBI both in the acute phase (66.5% vs. 21.1%; P = .0001) and the late phase (30.0% vs. 4.5%; P = .0001).

In further support of APBI, cosmetic results, as measured by the Harvard Breast Cosmesis Scale, were significantly better in the APBI group than in the WBI group. Both physicians and patients were significantly more likely to report good or excellent cosmetic results with APBI than WBI.

“APBI might be considered a standard alternative to WBI in low risk and very low risk early breast cancer patients,” Dr. Meattini concluded.

The investigators reported no disclosures.

SOURCE: Meattini et al. SABCS. 2019 Dec 12. Abstract GS4-06.

SAN ANTONIO – For patients with early, low-risk breast cancer, accelerated partial breast irradiation (APBI) may be considered a standard alternative to whole breast irradiation, according to investigators.

Will Pass/MDedge News

This conclusion was based on 10-year follow-up results from the APBI IMRT Florence phase III trial, which showed that APBI was associated with significantly fewer adverse events and better cosmetic results than whole breast irradiation without increasing risks of tumor recurrence or mortality, reported lead author Irco Meattini, MD, of the University of Florence, Italy, and colleagues.

“As we well know, recent developments in radiation oncology ... show a move toward a deescalation strategy for early breast cancer, including accelerated and nonaccelerated partial breast irradiation,” Dr. Meattini said during a presentation at the San Antonio Breast Cancer Symposium. “What we have learned from [previous] phase 3 trials [is that with adequate patient selection for] partial breast irradiation, safety profile and cosmetic outcome are strongly associated with technique – the approach, the dose, the number of fractions per day, and the total dose.”

The current phase 3 trial, which enrolled 520 patients with early breast cancer, aimed to determine long-term efficacy, safety, and cosmetic outcomes for partial versus whole breast irradiation. All patients enrolled were at least 40 years of age and had a maximum pathological tumor size of 25 mm. Patients were randomized in a 1:1 ratio to receive either whole breast irradiation (WBI) at a dose of 50 Gy in 25 fractions, followed by 10 Gy in five fractions delivered to the tumor bed; or APBI, which was delivered to the tumor bed at a dose of 30 Gy in five daily fractions.

The primary endpoint was ipsilateral breast tumor recurrence (IBTR). Secondary endpoints were overall survival, breast cancer–specific survival, distant metastasis-free survival, locoregional recurrences, and contralateral breast cancer. Adverse events and cosmesis also were evaluated.

Five-year results, previously reported, revealed no significant difference in survival rates or IBTR between treatment techniques, and results of the present 10-year analysis maintained these findings. Between groups, no significant differences were observed in any of the primary or secondary endpoints, suggesting that major efficacy outcomes were unaffected by type of irradiation delivered.

While major efficacy endpoints were comparable between groups, safety profiles and cosmetic results differed significantly.

Adverse events of all levels of severity were significantly more common with WBI than APBI. Grade 2 or higher acute adverse events occurred in 37.7% of patients treated with WBI, compared with just 2.0% of patients treated with APBI (P = .0001). The rate of grade 2 or higher adverse events was also significantly higher in the WBI group than in the APBI group in the late setting, albeit with a narrower margin than in the acute setting (2.7% vs 0%; P = .015). Skin toxicity rates followed a similar pattern, favoring APBI both in the acute phase (66.5% vs. 21.1%; P = .0001) and the late phase (30.0% vs. 4.5%; P = .0001).

In further support of APBI, cosmetic results, as measured by the Harvard Breast Cosmesis Scale, were significantly better in the APBI group than in the WBI group. Both physicians and patients were significantly more likely to report good or excellent cosmetic results with APBI than WBI.

“APBI might be considered a standard alternative to WBI in low risk and very low risk early breast cancer patients,” Dr. Meattini concluded.

The investigators reported no disclosures.

SOURCE: Meattini et al. SABCS. 2019 Dec 12. Abstract GS4-06.

SAN ANTONIO – For patients with early-stage triple-negative breast cancer, adding capecitabine to systemic treatment may extend overall survival, according to a meta-analysis involving more than 15,000 patients.

Will Pass/MDedge News

Although a variety of trials have tested capecitabine therapy for early-stage breast cancer, this study is the first to evaluate individual patient data across trials, reported lead author Marion van Mackelenbergh, MD, of University Medical Center Schleswig-Holstein in Kiel, Germany, and colleagues.

According to Dr. Mackelenbergh, who presented findings at the San Antonio Breast Cancer Symposium, the two previous literature-based meta-analyses of capecitabine for patients with early-stage breast cancer reported conflicting results; the first study suggested that capecitabine had no benefit as a neoadjuvant therapy, whereas the second study concluded that capecitabine could improve disease-free survival (DFS).

To build upon these findings, the primary objective of the present meta-analysis was to determine how treatment with capecitabine impacts DFS, Dr. Mackelenbergh said. A variety of secondary objectives were also evaluated, including overall survival and a possible interaction between capecitabine-specific toxicities and treatment effects.

The analysis involved 15,457 patients from 12 randomized prospective clinical trials, of whom about half (n = 7,477) were treated in control arms. Slightly more than half (55.9%) of the patients had stage II tumors and about three-fourths (74.0%) presented with nodal involvement. About two-thirds of patients (66.0%) had estrogen receptor–positive disease, about half (56.9%) were progesterone receptor–positive, and 15.1% were human epidermal growth factor receptor 2–positive. Most of the patients (81.8%) were treated with chemotherapy in the adjuvant setting, whereas the remainder (18.2%) received neoadjuvant therapy.

Cox regression analysis involving all patients in the dataset showed that capecitabine was not associated with a significant improvement in DFS, nor was a significant improvement seen in trials that compared capecitabine against other treatment options. In contrast, adding capecitabine to systemic treatment supported a modest but significant improvement in DFS (hazard ratio, 0.888; P = .0005).

Across all patients, capecitabine was associated with an overall survival advantage, although this benefit was relatively small, with a hazard ratio of 0.892. The overall survival benefit became more pronounced when capecitabine was added to systemic treatment (HR, 0.837).

Of clinical importance, biological subtype analysis showed that only patients with triple-negative breast cancer were deriving survival benefit from capecitabine, particularly when capecitabine was added to systemic treatment. Among patients with triple-negative disease, a 17% overall survival benefit was associated with capecitabine (HR, 0.828). When capecitabine was added to systemic treatment, this survival advantage improved to 22% (HR, 0.778).

No relationship was found between capecitabine-specific toxicity (mucositis, hand-foot syndrome, diarrhea) and patient outcome.

“It can be concluded that the addition of capecitabine to other systemic treatment may be recommended for triple-negative breast cancer patients,” Dr. Mackelenbergh said.

Will Pass/MDedge News

Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City agreed with this conclusion.

“Routine use of capecitabine as a component of neoadjuvant or adjuvant regimens in unselected patients cannot be endorsed,” Dr. Sharma said. “However, capecitabine should be considered in patients with triple-negative breast cancer, especially if response to neoadjuvant chemotherapy is utilized as a way to identify eligible patients so as to limit exposure and toxicity to those at the highest risk.”

In terms of the future, Dr. Sharma suggested that research is needed to determine the potential for adjuvant capecitabine among patients with triple-negative breast cancer who have received platinum-based chemotherapy and/or immune checkpoint inhibitor therapy as part of their neoadjuvant regimen. In addition, investigators should evaluate capecitabine efficacy in terms of residual disease and identify relevant predictive biomarkers, Dr. Sharma said.

The investigators reported relationships with Amgen, Lilly, Pfizer, and others.

SOURCE: van Mackelenbergh M et al. SABCS 2019, Abstract GS1-07.

SAN ANTONIO – For patients with early-stage triple-negative breast cancer, adding capecitabine to systemic treatment may extend overall survival, according to a meta-analysis involving more than 15,000 patients.

Will Pass/MDedge News

Although a variety of trials have tested capecitabine therapy for early-stage breast cancer, this study is the first to evaluate individual patient data across trials, reported lead author Marion van Mackelenbergh, MD, of University Medical Center Schleswig-Holstein in Kiel, Germany, and colleagues.

According to Dr. Mackelenbergh, who presented findings at the San Antonio Breast Cancer Symposium, the two previous literature-based meta-analyses of capecitabine for patients with early-stage breast cancer reported conflicting results; the first study suggested that capecitabine had no benefit as a neoadjuvant therapy, whereas the second study concluded that capecitabine could improve disease-free survival (DFS).

To build upon these findings, the primary objective of the present meta-analysis was to determine how treatment with capecitabine impacts DFS, Dr. Mackelenbergh said. A variety of secondary objectives were also evaluated, including overall survival and a possible interaction between capecitabine-specific toxicities and treatment effects.

The analysis involved 15,457 patients from 12 randomized prospective clinical trials, of whom about half (n = 7,477) were treated in control arms. Slightly more than half (55.9%) of the patients had stage II tumors and about three-fourths (74.0%) presented with nodal involvement. About two-thirds of patients (66.0%) had estrogen receptor–positive disease, about half (56.9%) were progesterone receptor–positive, and 15.1% were human epidermal growth factor receptor 2–positive. Most of the patients (81.8%) were treated with chemotherapy in the adjuvant setting, whereas the remainder (18.2%) received neoadjuvant therapy.

Cox regression analysis involving all patients in the dataset showed that capecitabine was not associated with a significant improvement in DFS, nor was a significant improvement seen in trials that compared capecitabine against other treatment options. In contrast, adding capecitabine to systemic treatment supported a modest but significant improvement in DFS (hazard ratio, 0.888; P = .0005).

Across all patients, capecitabine was associated with an overall survival advantage, although this benefit was relatively small, with a hazard ratio of 0.892. The overall survival benefit became more pronounced when capecitabine was added to systemic treatment (HR, 0.837).

Of clinical importance, biological subtype analysis showed that only patients with triple-negative breast cancer were deriving survival benefit from capecitabine, particularly when capecitabine was added to systemic treatment. Among patients with triple-negative disease, a 17% overall survival benefit was associated with capecitabine (HR, 0.828). When capecitabine was added to systemic treatment, this survival advantage improved to 22% (HR, 0.778).

No relationship was found between capecitabine-specific toxicity (mucositis, hand-foot syndrome, diarrhea) and patient outcome.

“It can be concluded that the addition of capecitabine to other systemic treatment may be recommended for triple-negative breast cancer patients,” Dr. Mackelenbergh said.

Will Pass/MDedge News

Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City agreed with this conclusion.

“Routine use of capecitabine as a component of neoadjuvant or adjuvant regimens in unselected patients cannot be endorsed,” Dr. Sharma said. “However, capecitabine should be considered in patients with triple-negative breast cancer, especially if response to neoadjuvant chemotherapy is utilized as a way to identify eligible patients so as to limit exposure and toxicity to those at the highest risk.”

In terms of the future, Dr. Sharma suggested that research is needed to determine the potential for adjuvant capecitabine among patients with triple-negative breast cancer who have received platinum-based chemotherapy and/or immune checkpoint inhibitor therapy as part of their neoadjuvant regimen. In addition, investigators should evaluate capecitabine efficacy in terms of residual disease and identify relevant predictive biomarkers, Dr. Sharma said.

The investigators reported relationships with Amgen, Lilly, Pfizer, and others.

SOURCE: van Mackelenbergh M et al. SABCS 2019, Abstract GS1-07.

SAN ANTONIO – For patients with early-stage triple-negative breast cancer, adding capecitabine to systemic treatment may extend overall survival, according to a meta-analysis involving more than 15,000 patients.

Will Pass/MDedge News

Although a variety of trials have tested capecitabine therapy for early-stage breast cancer, this study is the first to evaluate individual patient data across trials, reported lead author Marion van Mackelenbergh, MD, of University Medical Center Schleswig-Holstein in Kiel, Germany, and colleagues.

According to Dr. Mackelenbergh, who presented findings at the San Antonio Breast Cancer Symposium, the two previous literature-based meta-analyses of capecitabine for patients with early-stage breast cancer reported conflicting results; the first study suggested that capecitabine had no benefit as a neoadjuvant therapy, whereas the second study concluded that capecitabine could improve disease-free survival (DFS).

To build upon these findings, the primary objective of the present meta-analysis was to determine how treatment with capecitabine impacts DFS, Dr. Mackelenbergh said. A variety of secondary objectives were also evaluated, including overall survival and a possible interaction between capecitabine-specific toxicities and treatment effects.

The analysis involved 15,457 patients from 12 randomized prospective clinical trials, of whom about half (n = 7,477) were treated in control arms. Slightly more than half (55.9%) of the patients had stage II tumors and about three-fourths (74.0%) presented with nodal involvement. About two-thirds of patients (66.0%) had estrogen receptor–positive disease, about half (56.9%) were progesterone receptor–positive, and 15.1% were human epidermal growth factor receptor 2–positive. Most of the patients (81.8%) were treated with chemotherapy in the adjuvant setting, whereas the remainder (18.2%) received neoadjuvant therapy.

Cox regression analysis involving all patients in the dataset showed that capecitabine was not associated with a significant improvement in DFS, nor was a significant improvement seen in trials that compared capecitabine against other treatment options. In contrast, adding capecitabine to systemic treatment supported a modest but significant improvement in DFS (hazard ratio, 0.888; P = .0005).

Across all patients, capecitabine was associated with an overall survival advantage, although this benefit was relatively small, with a hazard ratio of 0.892. The overall survival benefit became more pronounced when capecitabine was added to systemic treatment (HR, 0.837).

Of clinical importance, biological subtype analysis showed that only patients with triple-negative breast cancer were deriving survival benefit from capecitabine, particularly when capecitabine was added to systemic treatment. Among patients with triple-negative disease, a 17% overall survival benefit was associated with capecitabine (HR, 0.828). When capecitabine was added to systemic treatment, this survival advantage improved to 22% (HR, 0.778).

No relationship was found between capecitabine-specific toxicity (mucositis, hand-foot syndrome, diarrhea) and patient outcome.

“It can be concluded that the addition of capecitabine to other systemic treatment may be recommended for triple-negative breast cancer patients,” Dr. Mackelenbergh said.

Will Pass/MDedge News

Invited discussant Priyanka Sharma, MD, of the University of Kansas Medical Center in Kansas City agreed with this conclusion.

“Routine use of capecitabine as a component of neoadjuvant or adjuvant regimens in unselected patients cannot be endorsed,” Dr. Sharma said. “However, capecitabine should be considered in patients with triple-negative breast cancer, especially if response to neoadjuvant chemotherapy is utilized as a way to identify eligible patients so as to limit exposure and toxicity to those at the highest risk.”

In terms of the future, Dr. Sharma suggested that research is needed to determine the potential for adjuvant capecitabine among patients with triple-negative breast cancer who have received platinum-based chemotherapy and/or immune checkpoint inhibitor therapy as part of their neoadjuvant regimen. In addition, investigators should evaluate capecitabine efficacy in terms of residual disease and identify relevant predictive biomarkers, Dr. Sharma said.

The investigators reported relationships with Amgen, Lilly, Pfizer, and others.

SOURCE: van Mackelenbergh M et al. SABCS 2019, Abstract GS1-07.

SAN ANTONIO – For postoperative breast cancer patients with a high risk of recurrence, the oral fluoropyrimidine-based drug S-1 could boost benefits of standard adjuvant treatment, based on results from the Japanese phase 3 POTENT trial.

Adding S-1 to endocrine therapy increased 5-year invasive disease-free survival (iDFS) by approximately 5% among patients with hormone receptor (HR)–positive, HER2-negative breast cancer, reported lead author Masakazu Toi, MD, PhD, of Kyoto University Hospital in Japan, and colleagues.

S-1 is a combination drug based on a biochemical modification of fluorouracil, with components aimed at potentiating activity and reducing gastrointestinal toxicity, Dr. Toi said at the San Antonio Breast Cancer Symposium.

Session moderator Carlos Arteaga, MD, of the University of Texas, Dallas, said that standard adjuvant treatment for breast cancer may evolve over the next few years, with S-1 representing one of several novel approaches currently under investigation.

“We’re all trying to optimize adjuvant endocrine therapy for patients that need it,” Dr. Arteaga said. “One approach is to add chemotherapy for those with a high-risk recurrence score. The other one is to … use CDK4/6 inhibitors in addition to endocrine therapy. … Clearly, endocrine therapy works in a majority of patients but in some it’s not sufficient, and we need to add a second intervention—that could be chemo in some cases, or it could be CDK4/6 inhibitors, if those trials pan out. This is another [strategy].”

The open-label POTENT trial was conducted at 139 centers in Japan, involving 1,932 patients with stage I-IIIB HR-positive, HER2-negative postoperative breast cancer who had intermediate to high risk of recurrence. Patients were enrolled within 1 year of surgery and 6 months of starting adjuvant therapy.

Patients were randomized at a 1:1 ratio to receive either standard endocrine therapy or endocrine therapy plus S-1, with S-1 given on a 2-weeks-on/1-week-off basis for 1 year. The primary endpoint was iDFS, defined as time from randomization to invasive disease recurrence, occurrence of second invasive cancer event, or death

After a median follow-up of 51.4 months, iDFS events were significantly more common in the control arm than the S-1 arm (15.9% vs. 10.6%; hazard ratio, 0.63; P = .0003). This translated to an estimated 5-year iDFS of 81.5% among patients who received endocrine therapy alone versus 86.9% among patients who also received S-1 (P less than .001).

While adding S-1 to endocrine therapy did increase the rate of adverse events, most instances were mild, leading the investigators to describe the novel regimen as “well tolerated and manageable.”

Among severe adverse events, grade 3-4 diarrhea and neutropenia were significantly more common in the S-1 arm than the control arm, with diarrhea occurring at a rate of 1.9% versus 0%, respectively, and neutropenia occurring at a rate of 7.5% versus 0.7%, respectively.

Based on these findings, Dr. Toi concluded that adding S-1 could be a viable option for improving outcomes in select patients.

“Our findings support the addition of S-1 to standard endocrine therapy in the postoperative adjuvant setting for patients with HR-positive/HER2-negative disease and an intermediate or higher risk of recurrence,” Dr. Toi said.

But according to invited discussant Priyanka Sharma, MD, of the University of Kansas, Kansas City, a place for S-1 in the clinic remains to be seen, partially because of potential differences in fluoropyrimidine drug metabolism based on ethnic background.

“The POTENT trial design does not allow us to discern in which setting and patient population addition of S-1 is most meaningful,” Dr. Sharma said. “This trial was done in Japan, so efficacy and toxicity in a non-Asian population is unclear.”

The study was funded by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation and Taiho Pharmaceutical. The investigators reported additional relationships with Bristol-Myers Squibb, Daiichi Sankyo, Genomic Health, and others.

SOURCE: Toi M et al. SABCS 2019, Abstract GS1-09.

SAN ANTONIO – For postoperative breast cancer patients with a high risk of recurrence, the oral fluoropyrimidine-based drug S-1 could boost benefits of standard adjuvant treatment, based on results from the Japanese phase 3 POTENT trial.

Adding S-1 to endocrine therapy increased 5-year invasive disease-free survival (iDFS) by approximately 5% among patients with hormone receptor (HR)–positive, HER2-negative breast cancer, reported lead author Masakazu Toi, MD, PhD, of Kyoto University Hospital in Japan, and colleagues.

S-1 is a combination drug based on a biochemical modification of fluorouracil, with components aimed at potentiating activity and reducing gastrointestinal toxicity, Dr. Toi said at the San Antonio Breast Cancer Symposium.

Session moderator Carlos Arteaga, MD, of the University of Texas, Dallas, said that standard adjuvant treatment for breast cancer may evolve over the next few years, with S-1 representing one of several novel approaches currently under investigation.

“We’re all trying to optimize adjuvant endocrine therapy for patients that need it,” Dr. Arteaga said. “One approach is to add chemotherapy for those with a high-risk recurrence score. The other one is to … use CDK4/6 inhibitors in addition to endocrine therapy. … Clearly, endocrine therapy works in a majority of patients but in some it’s not sufficient, and we need to add a second intervention—that could be chemo in some cases, or it could be CDK4/6 inhibitors, if those trials pan out. This is another [strategy].”

The open-label POTENT trial was conducted at 139 centers in Japan, involving 1,932 patients with stage I-IIIB HR-positive, HER2-negative postoperative breast cancer who had intermediate to high risk of recurrence. Patients were enrolled within 1 year of surgery and 6 months of starting adjuvant therapy.

Patients were randomized at a 1:1 ratio to receive either standard endocrine therapy or endocrine therapy plus S-1, with S-1 given on a 2-weeks-on/1-week-off basis for 1 year. The primary endpoint was iDFS, defined as time from randomization to invasive disease recurrence, occurrence of second invasive cancer event, or death

After a median follow-up of 51.4 months, iDFS events were significantly more common in the control arm than the S-1 arm (15.9% vs. 10.6%; hazard ratio, 0.63; P = .0003). This translated to an estimated 5-year iDFS of 81.5% among patients who received endocrine therapy alone versus 86.9% among patients who also received S-1 (P less than .001).

While adding S-1 to endocrine therapy did increase the rate of adverse events, most instances were mild, leading the investigators to describe the novel regimen as “well tolerated and manageable.”

Among severe adverse events, grade 3-4 diarrhea and neutropenia were significantly more common in the S-1 arm than the control arm, with diarrhea occurring at a rate of 1.9% versus 0%, respectively, and neutropenia occurring at a rate of 7.5% versus 0.7%, respectively.

Based on these findings, Dr. Toi concluded that adding S-1 could be a viable option for improving outcomes in select patients.

“Our findings support the addition of S-1 to standard endocrine therapy in the postoperative adjuvant setting for patients with HR-positive/HER2-negative disease and an intermediate or higher risk of recurrence,” Dr. Toi said.

But according to invited discussant Priyanka Sharma, MD, of the University of Kansas, Kansas City, a place for S-1 in the clinic remains to be seen, partially because of potential differences in fluoropyrimidine drug metabolism based on ethnic background.

“The POTENT trial design does not allow us to discern in which setting and patient population addition of S-1 is most meaningful,” Dr. Sharma said. “This trial was done in Japan, so efficacy and toxicity in a non-Asian population is unclear.”

The study was funded by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation and Taiho Pharmaceutical. The investigators reported additional relationships with Bristol-Myers Squibb, Daiichi Sankyo, Genomic Health, and others.

SOURCE: Toi M et al. SABCS 2019, Abstract GS1-09.

SAN ANTONIO – For postoperative breast cancer patients with a high risk of recurrence, the oral fluoropyrimidine-based drug S-1 could boost benefits of standard adjuvant treatment, based on results from the Japanese phase 3 POTENT trial.

Adding S-1 to endocrine therapy increased 5-year invasive disease-free survival (iDFS) by approximately 5% among patients with hormone receptor (HR)–positive, HER2-negative breast cancer, reported lead author Masakazu Toi, MD, PhD, of Kyoto University Hospital in Japan, and colleagues.

S-1 is a combination drug based on a biochemical modification of fluorouracil, with components aimed at potentiating activity and reducing gastrointestinal toxicity, Dr. Toi said at the San Antonio Breast Cancer Symposium.

Session moderator Carlos Arteaga, MD, of the University of Texas, Dallas, said that standard adjuvant treatment for breast cancer may evolve over the next few years, with S-1 representing one of several novel approaches currently under investigation.

“We’re all trying to optimize adjuvant endocrine therapy for patients that need it,” Dr. Arteaga said. “One approach is to add chemotherapy for those with a high-risk recurrence score. The other one is to … use CDK4/6 inhibitors in addition to endocrine therapy. … Clearly, endocrine therapy works in a majority of patients but in some it’s not sufficient, and we need to add a second intervention—that could be chemo in some cases, or it could be CDK4/6 inhibitors, if those trials pan out. This is another [strategy].”

The open-label POTENT trial was conducted at 139 centers in Japan, involving 1,932 patients with stage I-IIIB HR-positive, HER2-negative postoperative breast cancer who had intermediate to high risk of recurrence. Patients were enrolled within 1 year of surgery and 6 months of starting adjuvant therapy.

Patients were randomized at a 1:1 ratio to receive either standard endocrine therapy or endocrine therapy plus S-1, with S-1 given on a 2-weeks-on/1-week-off basis for 1 year. The primary endpoint was iDFS, defined as time from randomization to invasive disease recurrence, occurrence of second invasive cancer event, or death

After a median follow-up of 51.4 months, iDFS events were significantly more common in the control arm than the S-1 arm (15.9% vs. 10.6%; hazard ratio, 0.63; P = .0003). This translated to an estimated 5-year iDFS of 81.5% among patients who received endocrine therapy alone versus 86.9% among patients who also received S-1 (P less than .001).

While adding S-1 to endocrine therapy did increase the rate of adverse events, most instances were mild, leading the investigators to describe the novel regimen as “well tolerated and manageable.”

Among severe adverse events, grade 3-4 diarrhea and neutropenia were significantly more common in the S-1 arm than the control arm, with diarrhea occurring at a rate of 1.9% versus 0%, respectively, and neutropenia occurring at a rate of 7.5% versus 0.7%, respectively.

Based on these findings, Dr. Toi concluded that adding S-1 could be a viable option for improving outcomes in select patients.

“Our findings support the addition of S-1 to standard endocrine therapy in the postoperative adjuvant setting for patients with HR-positive/HER2-negative disease and an intermediate or higher risk of recurrence,” Dr. Toi said.

But according to invited discussant Priyanka Sharma, MD, of the University of Kansas, Kansas City, a place for S-1 in the clinic remains to be seen, partially because of potential differences in fluoropyrimidine drug metabolism based on ethnic background.

“The POTENT trial design does not allow us to discern in which setting and patient population addition of S-1 is most meaningful,” Dr. Sharma said. “This trial was done in Japan, so efficacy and toxicity in a non-Asian population is unclear.”

The study was funded by the Comprehensive Support Project for Oncology Research of the Public Health Research Foundation and Taiho Pharmaceutical. The investigators reported additional relationships with Bristol-Myers Squibb, Daiichi Sankyo, Genomic Health, and others.

SOURCE: Toi M et al. SABCS 2019, Abstract GS1-09.

Patient-reported outcomes support pembrolizumab plus chemotherapy for first-line treatment of metastatic non–small cell lung cancer (NSCLC), based on results from the KEYNOTE-407 trial.

At week 18, patients given pembrolizumab more often reported clinically meaningful health-related quality of life improvements than those in the placebo group, according to lead author Julien Mazieres, MD, PhD, of Paul Sabatier University in Toulouse, France, and colleagues.

Writing in the Journal of Clinical Oncology, the investigators explained that these findings build upon previously published results from KEYNOTE-407, which showed that adding pembrolizumab to chemotherapy in the first line could extend both progression-free and overall survival among patients with NSCLC. The benefits to quality of life associated with pembrolizumab align with similar findings from the KEYNOTE-024 and KEYNOTE-189 trials, they added.

The present analysis involved 559 patients with treatment-naive metastatic NSCLC. Patients were randomized to receive 4 cycles of placebo or pembrolizumab once every 3 weeks with carboplatin-based chemotherapy, followed by pembrolizumab or placebo for an additional 31 cycles. Health-related quality of life was assessed by two measures: the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and QLQ–Lung Cancer Module 13 (QLQ-LC13).

Of the 559 patients enrolled, 554 completed at least one QLQ-C30 assessment and 553 completed at least one QLQ-LC13 assessment. These quality of life scores were compared temporally within treatment groups, from baseline to week 9 and week 18, and between groups. The investigators also analyzed median time to deterioration in chest pain, cough, and dyspnea.

Results showed that patients in the pembrolizumab group had statistically significant improvements in patient-reported outcomes over time and more frequently reported improvements than patients in the placebo group. Specifically, in the pembrolizumab group, least-squares mean score improved from baseline to week 9 (1.8) and week 18 (4.3); in comparison, least-squares mean score deteriorated in the placebo group from baseline to week 9 (–1.8) and week 18 (–0.57). Compared with placebo, treatment with pembrolizumab was associated with a least-squares mean change of 3.6 at week 9 (nominal P = .0337) and 4.9 at week 18 (nominal P = .0060). Stated differently, at week 18, compared with placebo, more patients in the pembrolizumab group reported clinically meaningful improvements in health-related quality of life (36.2% vs. 27.7%), and relatively fewer reported deterioration (22.8% vs. 31.3%). Median time to deterioration in symptoms was not reached in either treatment arm.

“These health-related quality of life findings, along with the improved efficacy (including overall survival benefit) of pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel, support its use as a first-line treatment of metastatic squamous NSCLC, regardless of programmed death–ligand 1 expression,” the investigators concluded.

The study was funded by Merck. The investigators reported additional relationships with Novartis, Genentech, Pfizer, and others.

SOURCE: Mazieres J et al. J Clin Oncol. 2019 Nov 21. doi: 10.1200/JCO.19.01348.

Patient-reported outcomes support pembrolizumab plus chemotherapy for first-line treatment of metastatic non–small cell lung cancer (NSCLC), based on results from the KEYNOTE-407 trial.

At week 18, patients given pembrolizumab more often reported clinically meaningful health-related quality of life improvements than those in the placebo group, according to lead author Julien Mazieres, MD, PhD, of Paul Sabatier University in Toulouse, France, and colleagues.

Writing in the Journal of Clinical Oncology, the investigators explained that these findings build upon previously published results from KEYNOTE-407, which showed that adding pembrolizumab to chemotherapy in the first line could extend both progression-free and overall survival among patients with NSCLC. The benefits to quality of life associated with pembrolizumab align with similar findings from the KEYNOTE-024 and KEYNOTE-189 trials, they added.

The present analysis involved 559 patients with treatment-naive metastatic NSCLC. Patients were randomized to receive 4 cycles of placebo or pembrolizumab once every 3 weeks with carboplatin-based chemotherapy, followed by pembrolizumab or placebo for an additional 31 cycles. Health-related quality of life was assessed by two measures: the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and QLQ–Lung Cancer Module 13 (QLQ-LC13).

Of the 559 patients enrolled, 554 completed at least one QLQ-C30 assessment and 553 completed at least one QLQ-LC13 assessment. These quality of life scores were compared temporally within treatment groups, from baseline to week 9 and week 18, and between groups. The investigators also analyzed median time to deterioration in chest pain, cough, and dyspnea.

Results showed that patients in the pembrolizumab group had statistically significant improvements in patient-reported outcomes over time and more frequently reported improvements than patients in the placebo group. Specifically, in the pembrolizumab group, least-squares mean score improved from baseline to week 9 (1.8) and week 18 (4.3); in comparison, least-squares mean score deteriorated in the placebo group from baseline to week 9 (–1.8) and week 18 (–0.57). Compared with placebo, treatment with pembrolizumab was associated with a least-squares mean change of 3.6 at week 9 (nominal P = .0337) and 4.9 at week 18 (nominal P = .0060). Stated differently, at week 18, compared with placebo, more patients in the pembrolizumab group reported clinically meaningful improvements in health-related quality of life (36.2% vs. 27.7%), and relatively fewer reported deterioration (22.8% vs. 31.3%). Median time to deterioration in symptoms was not reached in either treatment arm.

“These health-related quality of life findings, along with the improved efficacy (including overall survival benefit) of pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel, support its use as a first-line treatment of metastatic squamous NSCLC, regardless of programmed death–ligand 1 expression,” the investigators concluded.

The study was funded by Merck. The investigators reported additional relationships with Novartis, Genentech, Pfizer, and others.

SOURCE: Mazieres J et al. J Clin Oncol. 2019 Nov 21. doi: 10.1200/JCO.19.01348.

Patient-reported outcomes support pembrolizumab plus chemotherapy for first-line treatment of metastatic non–small cell lung cancer (NSCLC), based on results from the KEYNOTE-407 trial.

At week 18, patients given pembrolizumab more often reported clinically meaningful health-related quality of life improvements than those in the placebo group, according to lead author Julien Mazieres, MD, PhD, of Paul Sabatier University in Toulouse, France, and colleagues.

Writing in the Journal of Clinical Oncology, the investigators explained that these findings build upon previously published results from KEYNOTE-407, which showed that adding pembrolizumab to chemotherapy in the first line could extend both progression-free and overall survival among patients with NSCLC. The benefits to quality of life associated with pembrolizumab align with similar findings from the KEYNOTE-024 and KEYNOTE-189 trials, they added.

The present analysis involved 559 patients with treatment-naive metastatic NSCLC. Patients were randomized to receive 4 cycles of placebo or pembrolizumab once every 3 weeks with carboplatin-based chemotherapy, followed by pembrolizumab or placebo for an additional 31 cycles. Health-related quality of life was assessed by two measures: the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire–Core 30 (QLQ-C30) and QLQ–Lung Cancer Module 13 (QLQ-LC13).

Of the 559 patients enrolled, 554 completed at least one QLQ-C30 assessment and 553 completed at least one QLQ-LC13 assessment. These quality of life scores were compared temporally within treatment groups, from baseline to week 9 and week 18, and between groups. The investigators also analyzed median time to deterioration in chest pain, cough, and dyspnea.

Results showed that patients in the pembrolizumab group had statistically significant improvements in patient-reported outcomes over time and more frequently reported improvements than patients in the placebo group. Specifically, in the pembrolizumab group, least-squares mean score improved from baseline to week 9 (1.8) and week 18 (4.3); in comparison, least-squares mean score deteriorated in the placebo group from baseline to week 9 (–1.8) and week 18 (–0.57). Compared with placebo, treatment with pembrolizumab was associated with a least-squares mean change of 3.6 at week 9 (nominal P = .0337) and 4.9 at week 18 (nominal P = .0060). Stated differently, at week 18, compared with placebo, more patients in the pembrolizumab group reported clinically meaningful improvements in health-related quality of life (36.2% vs. 27.7%), and relatively fewer reported deterioration (22.8% vs. 31.3%). Median time to deterioration in symptoms was not reached in either treatment arm.

“These health-related quality of life findings, along with the improved efficacy (including overall survival benefit) of pembrolizumab plus carboplatin and paclitaxel/nab-paclitaxel, support its use as a first-line treatment of metastatic squamous NSCLC, regardless of programmed death–ligand 1 expression,” the investigators concluded.

The study was funded by Merck. The investigators reported additional relationships with Novartis, Genentech, Pfizer, and others.

SOURCE: Mazieres J et al. J Clin Oncol. 2019 Nov 21. doi: 10.1200/JCO.19.01348.