A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.

The findings confirm clinical observations of disease heterogeneity, and highlight that PN “involves a spectrum of neuroimmune dysfunction, where patients can be at either end of the spectrum [toward either immune or neural dysregulation],” said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”

He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.

To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.

The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.

One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.

The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.

In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)

There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.

“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”

The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”

Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.

Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.

Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.

PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.

Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.

A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.

The findings confirm clinical observations of disease heterogeneity, and highlight that PN “involves a spectrum of neuroimmune dysfunction, where patients can be at either end of the spectrum [toward either immune or neural dysregulation],” said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”

He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.

To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.

The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.

One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.

The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.

In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)

There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.

“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”

The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”

Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.

Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.

Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.

PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.

Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.

A cluster analysis of circulating plasma biomarkers in prurigo nodularis (PN) has identified two disease endotypes with inflammatory and noninflammatory biomarker profiles.

The findings confirm clinical observations of disease heterogeneity, and highlight that PN “involves a spectrum of neuroimmune dysfunction, where patients can be at either end of the spectrum [toward either immune or neural dysregulation],” said senior author Shawn G. Kwatra, MD, of the department of dermatology at Johns Hopkins University, Baltimore. “This is the beginning of personalized medicine in prurigo nodularis.”

He and others have long observed significant clinical heterogeneity both in the presentation of PN – with the nodules in African American patients, for instance, appearing larger, thicker, and more fibrotic – and in patients’ response to immunomodulating and neuromodulating therapies.

To avoid the introduction of bias, the researchers used an unsupervised machine-learning approach to analyze the levels of 12 inflammatory biomarkers in 20 patients with PN and in matched healthy controls. The biomarkers were chosen based on their demonstrated dysregulation in PN and other inflammatory dermatoses.

The researchers then conducted a population-level analysis using multicenter electronic medical record data to explore inflammatory markers and verify findings from the cluster analysis. The study was published online Oct. 27, 2021, in the Journal of Investigative Dermatology.

One cluster of the 20 patients had higher levels of nine inflammatory biomarkers representing multiple immune axes: Higher interleukin-1 alpha, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, and IL-25. This cluster had a higher percentage of Black patients, a higher severity of itch, and lower quality of life scores, the authors report in the preprint.

The other cluster – without such an inflammatory profile – had fewer Black patients and a higher percentage of patients with myelopathy (e.g. spinal stenosis, spinal trauma, degenerative disc disease). The rates of inflammatory comorbidities and of immune- and neuromodulating treatments at the time of blood draw were relatively equivalent between the two clusters.

In the subsequent population-level analysis, using data from a global health research network of EMRs from almost 50 health care organizations, Black patients with PN were found to have higher erythrocyte sedimentation rate, C-reactive protein, ferritin, and eosinophils, and lower transferrin, than White patients with PN. (The analysis included only Black and White patients.)

There are no Food and Drug Administration–approved therapies for PN, and “clinicians need to be really creative in managing these patients,” Dr. Kwatra said.

“There may be suggestions at the bedside that patients have more immune dysregulation, or maybe I’ll see increased circulating blood eosinophils,” he said. “And there are those who don’t seem to have any immune dysregulation and have more features of neurosensitization ... who may have a history of neck pain or back injury.”

The existence of endotypes in PN suggests that patients may benefit from personalized therapies with either immunomodulating or neuromodulating treatments, he and his colleagues wrote. “Further neuroimmune phenotyping studies of PN may pave the way for a future precision medicine management approach.”

Studies of PN conducted in Europe have been almost exclusively in White patients, Dr. Kwatra noted, even though PN has been shown to disproportionately affect Black and other racial/ethnic-minority patients.

Black patients with PN were found to have the highest all-cause mortality over 20 years post diagnosis in a separate analysis of over 22,000 patients with PN. Using data from the same health research network, Dr. Kwatra and coinvestigators stratified patients by race/ethnicity and compared each subgroup with a corresponding subgroup of similar race/ethnicity to control for inherent differences in mortality.

Overall, patients with PN had higher all-cause mortality than controls (hazard ratio, 1.70), likely because of a high comorbidity burden, they wrote in their research letter. Black patients with PN had the highest mortality (HR, 2.07), followed by White (HR, 1.74) and Hispanic (HR, 1.62) patients.

PN may exacerbate existing racial disparities in the social determinants of health, and Black patients may suffer from greater systemic inflammation, Dr. Kwatra and coauthors wrote. Certainly, he said, these findings, as well as the finding of a distinct inflammatory signature in Black patients with PN, support “that the disease burden is much higher” in these patients.

Dr Kwatra disclosed that he is an advisory board member/consultant for Celldex Therapeutics, Galderma, Incyte, Pfizer, Regeneron, and Kiniksa Pharmaceuticals and has received grant funding from several companies. His research is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Grants from the Dermatology Foundation and the Skin of Color Society also helped fund the cluster analysis.

Key clinical point: Palbociclib dose reduction occurs in real-world practice among patients with advanced breast cancer (BC) and has no negative clinical outcomes. It is more common in older patients, with no effect on survival.

Major finding: Overall, palbociclib dose reduction occurred in 33% of patients, with median time-to-next treatment (P < .001) and median overall survival (OS; P = .003) significantly longer in patients with vs without dose reduction. Dose reductions were more common in patients aged ≥70 years vs <70 years (P = .041), with no effect observed on median OS (P = .051).

Study details: This real-world analysis included 598 patients (median age, 64 years) with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced BC who were treated with palbociclib combined with either fulvestrant or aromatase inhibitors.

Disclosures: This study was funded by Dutch health insurer VGZ. The authors declared no conflict of interests.

Source: Ismail RK et al. Breast. 2021 Nov 17. doi: 10.1016/j.breast.2021.11.013.

Key clinical point: Palbociclib dose reduction occurs in real-world practice among patients with advanced breast cancer (BC) and has no negative clinical outcomes. It is more common in older patients, with no effect on survival.

Major finding: Overall, palbociclib dose reduction occurred in 33% of patients, with median time-to-next treatment (P < .001) and median overall survival (OS; P = .003) significantly longer in patients with vs without dose reduction. Dose reductions were more common in patients aged ≥70 years vs <70 years (P = .041), with no effect observed on median OS (P = .051).

Study details: This real-world analysis included 598 patients (median age, 64 years) with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced BC who were treated with palbociclib combined with either fulvestrant or aromatase inhibitors.

Disclosures: This study was funded by Dutch health insurer VGZ. The authors declared no conflict of interests.

Source: Ismail RK et al. Breast. 2021 Nov 17. doi: 10.1016/j.breast.2021.11.013.

Key clinical point: Palbociclib dose reduction occurs in real-world practice among patients with advanced breast cancer (BC) and has no negative clinical outcomes. It is more common in older patients, with no effect on survival.

Major finding: Overall, palbociclib dose reduction occurred in 33% of patients, with median time-to-next treatment (P < .001) and median overall survival (OS; P = .003) significantly longer in patients with vs without dose reduction. Dose reductions were more common in patients aged ≥70 years vs <70 years (P = .041), with no effect observed on median OS (P = .051).

Study details: This real-world analysis included 598 patients (median age, 64 years) with hormone receptor-positive, human epidermal growth factor receptor 2-negative, advanced BC who were treated with palbociclib combined with either fulvestrant or aromatase inhibitors.

Disclosures: This study was funded by Dutch health insurer VGZ. The authors declared no conflict of interests.

Source: Ismail RK et al. Breast. 2021 Nov 17. doi: 10.1016/j.breast.2021.11.013.

Key clinical point: The possibility of cancer-related or pathologic vertebral fracture should be considered in women with invasive breast cancer who received endocrine therapy, particularly those with, advanced stage cancer history where every 1 in 3 incident vetrtebral fractures was a pathologic fracture.

.Major finding: Overall, 21.2% of vertebral fractures were pathologic with the chances of vertebral fractures being pathologic higher in patients with stage 3-4 vs initial stage 1 and 2 breast cancer (41.2% vs 17.2%; P < .05).

Study details: Findings are from a cohort study including 5010 women with newly-diagnosed invasive breast cancer who received endocrine therapy and were followed up from invasive breast cancer diagnosis to 10 years or until September 30, 2015, for incident bone fracture.

Disclosures: This study was funded by the National Cancer Institute, National Institutes of Health, and the Research Program on Genes, Environment and Health of Kaiser Permanente Northern California. The authors declared no conflicts of interest.

Source: Lo JC et al. JAMA Netw Open. 2021 Nov 17. doi: 10.1001/jamanetworkopen.2021.33861.

Key clinical point: The possibility of cancer-related or pathologic vertebral fracture should be considered in women with invasive breast cancer who received endocrine therapy, particularly those with, advanced stage cancer history where every 1 in 3 incident vetrtebral fractures was a pathologic fracture.

.Major finding: Overall, 21.2% of vertebral fractures were pathologic with the chances of vertebral fractures being pathologic higher in patients with stage 3-4 vs initial stage 1 and 2 breast cancer (41.2% vs 17.2%; P < .05).

Study details: Findings are from a cohort study including 5010 women with newly-diagnosed invasive breast cancer who received endocrine therapy and were followed up from invasive breast cancer diagnosis to 10 years or until September 30, 2015, for incident bone fracture.

Disclosures: This study was funded by the National Cancer Institute, National Institutes of Health, and the Research Program on Genes, Environment and Health of Kaiser Permanente Northern California. The authors declared no conflicts of interest.

Source: Lo JC et al. JAMA Netw Open. 2021 Nov 17. doi: 10.1001/jamanetworkopen.2021.33861.

Key clinical point: The possibility of cancer-related or pathologic vertebral fracture should be considered in women with invasive breast cancer who received endocrine therapy, particularly those with, advanced stage cancer history where every 1 in 3 incident vetrtebral fractures was a pathologic fracture.

.Major finding: Overall, 21.2% of vertebral fractures were pathologic with the chances of vertebral fractures being pathologic higher in patients with stage 3-4 vs initial stage 1 and 2 breast cancer (41.2% vs 17.2%; P < .05).

Study details: Findings are from a cohort study including 5010 women with newly-diagnosed invasive breast cancer who received endocrine therapy and were followed up from invasive breast cancer diagnosis to 10 years or until September 30, 2015, for incident bone fracture.

Disclosures: This study was funded by the National Cancer Institute, National Institutes of Health, and the Research Program on Genes, Environment and Health of Kaiser Permanente Northern California. The authors declared no conflicts of interest.

Source: Lo JC et al. JAMA Netw Open. 2021 Nov 17. doi: 10.1001/jamanetworkopen.2021.33861.

Key clinical point: Rupacarib did not show clinical benefits in the overall cohort of patients with metastatic breast cancer, but a small proportion of patients with high loss of heterozygosity (LOH) scores and no mutations in germline BReast CAncer genes 1 and 2 (BRCA1/2) seemed to benefit.

Major finding: Investigator-assessed clinical benefit rate was 13.5% (95% CI, 4.5%-28.8%) in the overall cohort, which was below the clinically relevant 20% mark. However, 5 patients achieved clinical benefits with rucaparib, with 2 of them with high LOH scores and no somatic BRCA1/2 mutation achieving a complete response of 12 months and 28.5 months, respectively.

Study details: Findings are from a phase 2 RUBY study including 40 adult patients with progressive human epidermal growth factor receptor 2-negative breast cancer with high LOH or nongermline BRCA1/2 mutation, who received at least 1 dose of rucaparib.

Disclosures: This study was funded by Clovis. The authors declared serving as speaker and advisor and/or receiving research grants, travel fees, consulting fees, and personal fees from various pharmaceutical companies.

Source: Patsouris A et al. Eur J Cancer. 2021 Nov 25. doi: 10.1016/j.ejca.2021.09.028.

Key clinical point: Rupacarib did not show clinical benefits in the overall cohort of patients with metastatic breast cancer, but a small proportion of patients with high loss of heterozygosity (LOH) scores and no mutations in germline BReast CAncer genes 1 and 2 (BRCA1/2) seemed to benefit.

Major finding: Investigator-assessed clinical benefit rate was 13.5% (95% CI, 4.5%-28.8%) in the overall cohort, which was below the clinically relevant 20% mark. However, 5 patients achieved clinical benefits with rucaparib, with 2 of them with high LOH scores and no somatic BRCA1/2 mutation achieving a complete response of 12 months and 28.5 months, respectively.

Study details: Findings are from a phase 2 RUBY study including 40 adult patients with progressive human epidermal growth factor receptor 2-negative breast cancer with high LOH or nongermline BRCA1/2 mutation, who received at least 1 dose of rucaparib.

Disclosures: This study was funded by Clovis. The authors declared serving as speaker and advisor and/or receiving research grants, travel fees, consulting fees, and personal fees from various pharmaceutical companies.

Source: Patsouris A et al. Eur J Cancer. 2021 Nov 25. doi: 10.1016/j.ejca.2021.09.028.

Key clinical point: Rupacarib did not show clinical benefits in the overall cohort of patients with metastatic breast cancer, but a small proportion of patients with high loss of heterozygosity (LOH) scores and no mutations in germline BReast CAncer genes 1 and 2 (BRCA1/2) seemed to benefit.

Major finding: Investigator-assessed clinical benefit rate was 13.5% (95% CI, 4.5%-28.8%) in the overall cohort, which was below the clinically relevant 20% mark. However, 5 patients achieved clinical benefits with rucaparib, with 2 of them with high LOH scores and no somatic BRCA1/2 mutation achieving a complete response of 12 months and 28.5 months, respectively.

Study details: Findings are from a phase 2 RUBY study including 40 adult patients with progressive human epidermal growth factor receptor 2-negative breast cancer with high LOH or nongermline BRCA1/2 mutation, who received at least 1 dose of rucaparib.

Disclosures: This study was funded by Clovis. The authors declared serving as speaker and advisor and/or receiving research grants, travel fees, consulting fees, and personal fees from various pharmaceutical companies.

Source: Patsouris A et al. Eur J Cancer. 2021 Nov 25. doi: 10.1016/j.ejca.2021.09.028.

Key clinical point: Including internal mammary node irradiation (IMNI) with regional node irradiation did not improve disease-free survival (DFS) significantly in the overall cohort of patients with node-positive breast cancer but benefited those with mediocentrally located tumors.

Major finding: The 7-year DFS rate was not significantly different between groups treated without vs with IMNI (81.9% vs 85.3%; hazard ratio [HR], 0.80; 95% CI, 0.57-1.14); however, it was significantly higher in patients with mediocentrally located tumor who were treated with vs without IMNI  (91.8% vs 81.6%; HR, 0.42; 95% CI, 0.22-0.82).

Study details: Findings are from phase 3 KROG 08-06 study including 735 patients with histologically confirmed, node-positive breast cancer who underwent breast-conservation surgery or mastectomy and axillary dissection and were randomly assigned to receive regional nodal irradiation with or without IMNI.

Disclosures: This work was supported by the Cancer Control of the Ministry of Health, Welfare, and Family Affairs, Korea. The authors declared no conflict of interests.

Source: Kim YB et al. JAMA Oncol. 2021 Oct 25. doi: 10.1001/jamaoncol.2021.6036.

Key clinical point: Including internal mammary node irradiation (IMNI) with regional node irradiation did not improve disease-free survival (DFS) significantly in the overall cohort of patients with node-positive breast cancer but benefited those with mediocentrally located tumors.

Major finding: The 7-year DFS rate was not significantly different between groups treated without vs with IMNI (81.9% vs 85.3%; hazard ratio [HR], 0.80; 95% CI, 0.57-1.14); however, it was significantly higher in patients with mediocentrally located tumor who were treated with vs without IMNI  (91.8% vs 81.6%; HR, 0.42; 95% CI, 0.22-0.82).

Study details: Findings are from phase 3 KROG 08-06 study including 735 patients with histologically confirmed, node-positive breast cancer who underwent breast-conservation surgery or mastectomy and axillary dissection and were randomly assigned to receive regional nodal irradiation with or without IMNI.

Disclosures: This work was supported by the Cancer Control of the Ministry of Health, Welfare, and Family Affairs, Korea. The authors declared no conflict of interests.

Source: Kim YB et al. JAMA Oncol. 2021 Oct 25. doi: 10.1001/jamaoncol.2021.6036.

Key clinical point: Including internal mammary node irradiation (IMNI) with regional node irradiation did not improve disease-free survival (DFS) significantly in the overall cohort of patients with node-positive breast cancer but benefited those with mediocentrally located tumors.

Major finding: The 7-year DFS rate was not significantly different between groups treated without vs with IMNI (81.9% vs 85.3%; hazard ratio [HR], 0.80; 95% CI, 0.57-1.14); however, it was significantly higher in patients with mediocentrally located tumor who were treated with vs without IMNI  (91.8% vs 81.6%; HR, 0.42; 95% CI, 0.22-0.82).

Study details: Findings are from phase 3 KROG 08-06 study including 735 patients with histologically confirmed, node-positive breast cancer who underwent breast-conservation surgery or mastectomy and axillary dissection and were randomly assigned to receive regional nodal irradiation with or without IMNI.

Disclosures: This work was supported by the Cancer Control of the Ministry of Health, Welfare, and Family Affairs, Korea. The authors declared no conflict of interests.

Source: Kim YB et al. JAMA Oncol. 2021 Oct 25. doi: 10.1001/jamaoncol.2021.6036.

Key clinical point: COVID-19 pandemic has changed breast cancer (BC) management strategies, with the use of neoadjuvant endocrine therapy (NET) increasing significantly during the pandemic; however, no effect was observed on BC stage at diagnosis.

Major finding: The use of NET increased significantly during COVID-19 pandemic period (P = .002), particularly in patients with stage I hormone receptor-positive, human epidermal growth factor receptor 2-negative BC where the use of NET increased from 10% pre-COVID-19 to 23% during COVID-19 pandemic (P = .001). The pandemic had no effect on clinical prognostic stage (P = 0.39) and proportion of patients with clinical nodal status+ BC (P = 0.38).

Study details: This was a retrospective chart review including patients with newly diagnosed BC who presented at Mayo Clinic, Rochester during (March-August 2020; n=197) or before (March-August 2019; n=376) the COVID-19 pandemic.

Disclosures: Dr. Boughey declared receiving research funding from Lilly and was on a data and safety monitoring board for Cairns Surgical.

Source: Tonneson JE et al. Ann Surg Oncol. 2021 Nov 23. doi: 10.1245/s10434-021-11088-6.

Key clinical point: COVID-19 pandemic has changed breast cancer (BC) management strategies, with the use of neoadjuvant endocrine therapy (NET) increasing significantly during the pandemic; however, no effect was observed on BC stage at diagnosis.

Major finding: The use of NET increased significantly during COVID-19 pandemic period (P = .002), particularly in patients with stage I hormone receptor-positive, human epidermal growth factor receptor 2-negative BC where the use of NET increased from 10% pre-COVID-19 to 23% during COVID-19 pandemic (P = .001). The pandemic had no effect on clinical prognostic stage (P = 0.39) and proportion of patients with clinical nodal status+ BC (P = 0.38).

Study details: This was a retrospective chart review including patients with newly diagnosed BC who presented at Mayo Clinic, Rochester during (March-August 2020; n=197) or before (March-August 2019; n=376) the COVID-19 pandemic.

Disclosures: Dr. Boughey declared receiving research funding from Lilly and was on a data and safety monitoring board for Cairns Surgical.

Source: Tonneson JE et al. Ann Surg Oncol. 2021 Nov 23. doi: 10.1245/s10434-021-11088-6.

Key clinical point: COVID-19 pandemic has changed breast cancer (BC) management strategies, with the use of neoadjuvant endocrine therapy (NET) increasing significantly during the pandemic; however, no effect was observed on BC stage at diagnosis.

Major finding: The use of NET increased significantly during COVID-19 pandemic period (P = .002), particularly in patients with stage I hormone receptor-positive, human epidermal growth factor receptor 2-negative BC where the use of NET increased from 10% pre-COVID-19 to 23% during COVID-19 pandemic (P = .001). The pandemic had no effect on clinical prognostic stage (P = 0.39) and proportion of patients with clinical nodal status+ BC (P = 0.38).

Study details: This was a retrospective chart review including patients with newly diagnosed BC who presented at Mayo Clinic, Rochester during (March-August 2020; n=197) or before (March-August 2019; n=376) the COVID-19 pandemic.

Disclosures: Dr. Boughey declared receiving research funding from Lilly and was on a data and safety monitoring board for Cairns Surgical.

Source: Tonneson JE et al. Ann Surg Oncol. 2021 Nov 23. doi: 10.1245/s10434-021-11088-6.

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) significantly benefitted from neoadjuvant chemotherapy with intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddPEC) vs paclitaxel plus non-pegylated liposomal doxorubicin (PM) plus carboplatin ([Cb], triple-negative BC only).

Major finding: Although the 4-year invasive disease-free survival (iDFS; P log-rank = .334) and overall survival (OS, P log-rank = .637) was not significantly different between iddEPC vs PM(Cb) arms in the entire cohort, the subgroup of patients with HR+/HER-2-, BC, showed significantly improved iDFS (hazard ratio [HR], 2.11; P log-rank = .025) and OS (HR,  3.26; P log-rank = .029).with iddEPC.

Study details: Findings are from phase 3 GeparOcto trial including 961 patients with high-risk early BC, who were randomly assigned 1:1 to receive iddEPC or PM(Cb), of which 706 patients completed treatment.

Disclosures: This study was funded by Roche, Amgen, TEVA, and Vifor. The authors reported receiving research grants, personal fees, consulting fees, honoraria and/ or travel support from the above companies and other sources.

Source: Schneeweiss A et al. Eur J Cancer. 2021 Nov 17. doi: 10.1016/j.ejca.2021.10.011.

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) significantly benefitted from neoadjuvant chemotherapy with intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddPEC) vs paclitaxel plus non-pegylated liposomal doxorubicin (PM) plus carboplatin ([Cb], triple-negative BC only).

Major finding: Although the 4-year invasive disease-free survival (iDFS; P log-rank = .334) and overall survival (OS, P log-rank = .637) was not significantly different between iddEPC vs PM(Cb) arms in the entire cohort, the subgroup of patients with HR+/HER-2-, BC, showed significantly improved iDFS (hazard ratio [HR], 2.11; P log-rank = .025) and OS (HR,  3.26; P log-rank = .029).with iddEPC.

Study details: Findings are from phase 3 GeparOcto trial including 961 patients with high-risk early BC, who were randomly assigned 1:1 to receive iddEPC or PM(Cb), of which 706 patients completed treatment.

Disclosures: This study was funded by Roche, Amgen, TEVA, and Vifor. The authors reported receiving research grants, personal fees, consulting fees, honoraria and/ or travel support from the above companies and other sources.

Source: Schneeweiss A et al. Eur J Cancer. 2021 Nov 17. doi: 10.1016/j.ejca.2021.10.011.

Key clinical point: Patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) significantly benefitted from neoadjuvant chemotherapy with intense dose-dense epirubicin, paclitaxel and cyclophosphamide (iddPEC) vs paclitaxel plus non-pegylated liposomal doxorubicin (PM) plus carboplatin ([Cb], triple-negative BC only).

Major finding: Although the 4-year invasive disease-free survival (iDFS; P log-rank = .334) and overall survival (OS, P log-rank = .637) was not significantly different between iddEPC vs PM(Cb) arms in the entire cohort, the subgroup of patients with HR+/HER-2-, BC, showed significantly improved iDFS (hazard ratio [HR], 2.11; P log-rank = .025) and OS (HR,  3.26; P log-rank = .029).with iddEPC.

Study details: Findings are from phase 3 GeparOcto trial including 961 patients with high-risk early BC, who were randomly assigned 1:1 to receive iddEPC or PM(Cb), of which 706 patients completed treatment.

Disclosures: This study was funded by Roche, Amgen, TEVA, and Vifor. The authors reported receiving research grants, personal fees, consulting fees, honoraria and/ or travel support from the above companies and other sources.

Source: Schneeweiss A et al. Eur J Cancer. 2021 Nov 17. doi: 10.1016/j.ejca.2021.10.011.

Key clinical point: Preliminary evidence indicated feasibility of LY2780301, a dual inhibitor of p70 ribosomal protein S6 kinase and protein kinase B (AKT) and paclitaxel combination in patients with hormone-resistant2 (HER2)-negative advanced breast cancer (BC).

Major finding: The recommended phase 2 dose was LY2780301 500 mg once daily + weekly paclitaxel 80 mg/m². The 6-month objective response rate for phase 2 was 63.9% (90% CI, 48.8-76.8) in the overall population and 55% (90% CI, 35.0-73.7) in phosphatidylinositol-3-kinase/AKT positive patients. The common drug-related adverse events were neuropathy, asthenia, ungual toxicity and pneumonitis.

Study details: Findings are from a prospective, multi-centred, phase 1b/2 TAKTIC trial including 48 patients with HER2-negative advanced BC with (phase 1B; n=12) or without (phase 2; n=36) previous cytotoxic treatment for advanced disease who were administered oral LY2780301 + intravenous paclitaxel.

Disclosures: This study was funded by the French National Cancer Institute, the Caritative Foundation and the Ligue Nationale Contre le Cancer. Three authors declared serving as advisory board member and/or receiving research grants and non-financial support from various pharmaceutical companies.

Source: Vicier C et al. Eur J Cancer. 2021 Nov 12. doi: 10.1016/j.ejca.2021.09.040.

Key clinical point: Preliminary evidence indicated feasibility of LY2780301, a dual inhibitor of p70 ribosomal protein S6 kinase and protein kinase B (AKT) and paclitaxel combination in patients with hormone-resistant2 (HER2)-negative advanced breast cancer (BC).

Major finding: The recommended phase 2 dose was LY2780301 500 mg once daily + weekly paclitaxel 80 mg/m². The 6-month objective response rate for phase 2 was 63.9% (90% CI, 48.8-76.8) in the overall population and 55% (90% CI, 35.0-73.7) in phosphatidylinositol-3-kinase/AKT positive patients. The common drug-related adverse events were neuropathy, asthenia, ungual toxicity and pneumonitis.

Study details: Findings are from a prospective, multi-centred, phase 1b/2 TAKTIC trial including 48 patients with HER2-negative advanced BC with (phase 1B; n=12) or without (phase 2; n=36) previous cytotoxic treatment for advanced disease who were administered oral LY2780301 + intravenous paclitaxel.

Disclosures: This study was funded by the French National Cancer Institute, the Caritative Foundation and the Ligue Nationale Contre le Cancer. Three authors declared serving as advisory board member and/or receiving research grants and non-financial support from various pharmaceutical companies.

Source: Vicier C et al. Eur J Cancer. 2021 Nov 12. doi: 10.1016/j.ejca.2021.09.040.

Key clinical point: Preliminary evidence indicated feasibility of LY2780301, a dual inhibitor of p70 ribosomal protein S6 kinase and protein kinase B (AKT) and paclitaxel combination in patients with hormone-resistant2 (HER2)-negative advanced breast cancer (BC).

Major finding: The recommended phase 2 dose was LY2780301 500 mg once daily + weekly paclitaxel 80 mg/m². The 6-month objective response rate for phase 2 was 63.9% (90% CI, 48.8-76.8) in the overall population and 55% (90% CI, 35.0-73.7) in phosphatidylinositol-3-kinase/AKT positive patients. The common drug-related adverse events were neuropathy, asthenia, ungual toxicity and pneumonitis.

Study details: Findings are from a prospective, multi-centred, phase 1b/2 TAKTIC trial including 48 patients with HER2-negative advanced BC with (phase 1B; n=12) or without (phase 2; n=36) previous cytotoxic treatment for advanced disease who were administered oral LY2780301 + intravenous paclitaxel.

Disclosures: This study was funded by the French National Cancer Institute, the Caritative Foundation and the Ligue Nationale Contre le Cancer. Three authors declared serving as advisory board member and/or receiving research grants and non-financial support from various pharmaceutical companies.

Source: Vicier C et al. Eur J Cancer. 2021 Nov 12. doi: 10.1016/j.ejca.2021.09.040.

Key clinical point: Dalpiciclib plus fulvestrant prolonged progression-free survival (PFS) compared with placebo+fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who progressed during or after endocrine therapy.

Major finding: Patients receiving dalpiciclib+fulvestrant showed significantly prolonged investigator-assessed progression-free survival than those who received placebo+fulvestrant (median, 15.7 months vs 7.2 months; hazard ratio, 0.42; P < .0001). Serious adverse events were reported by 5.8% vs 6.7% of patients recieving dalpiciclib+fulvestrant vs placebo+fulvestrant.

Study details: Findings are interim results from phase 3 DAWNA-1 trial, including 361 patients with HR-positive, HER2-negative locally advanced breast cancer who progressed on endocrine therapy and were randomly assigned to dalpiciclib+fulvestrant or placebo+fulvestrant.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals. The authors reported receiving research grants, advisory fees from Hengrui and other sources. Four authors declared being employees of Hengrui.

Source: Xu B et al. Nat Med. 2021 Nov 4. doi: 10.1038/s41591-021-01562-9.

Key clinical point: Dalpiciclib plus fulvestrant prolonged progression-free survival (PFS) compared with placebo+fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who progressed during or after endocrine therapy.

Major finding: Patients receiving dalpiciclib+fulvestrant showed significantly prolonged investigator-assessed progression-free survival than those who received placebo+fulvestrant (median, 15.7 months vs 7.2 months; hazard ratio, 0.42; P < .0001). Serious adverse events were reported by 5.8% vs 6.7% of patients recieving dalpiciclib+fulvestrant vs placebo+fulvestrant.

Study details: Findings are interim results from phase 3 DAWNA-1 trial, including 361 patients with HR-positive, HER2-negative locally advanced breast cancer who progressed on endocrine therapy and were randomly assigned to dalpiciclib+fulvestrant or placebo+fulvestrant.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals. The authors reported receiving research grants, advisory fees from Hengrui and other sources. Four authors declared being employees of Hengrui.

Source: Xu B et al. Nat Med. 2021 Nov 4. doi: 10.1038/s41591-021-01562-9.

Key clinical point: Dalpiciclib plus fulvestrant prolonged progression-free survival (PFS) compared with placebo+fulvestrant in patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who progressed during or after endocrine therapy.

Major finding: Patients receiving dalpiciclib+fulvestrant showed significantly prolonged investigator-assessed progression-free survival than those who received placebo+fulvestrant (median, 15.7 months vs 7.2 months; hazard ratio, 0.42; P < .0001). Serious adverse events were reported by 5.8% vs 6.7% of patients recieving dalpiciclib+fulvestrant vs placebo+fulvestrant.

Study details: Findings are interim results from phase 3 DAWNA-1 trial, including 361 patients with HR-positive, HER2-negative locally advanced breast cancer who progressed on endocrine therapy and were randomly assigned to dalpiciclib+fulvestrant or placebo+fulvestrant.

Disclosures: This study was funded by Jiangsu Hengrui Pharmaceuticals. The authors reported receiving research grants, advisory fees from Hengrui and other sources. Four authors declared being employees of Hengrui.

Source: Xu B et al. Nat Med. 2021 Nov 4. doi: 10.1038/s41591-021-01562-9.

Key clinical point: Final 12-year results from the PROMISE-GIM6 study reassures safety of concurrent administration of gonadotropin-releasing hormone agonist (GnRHa), triptorelin during chemotherapy in premenopausal women with early breast cancer (BC).

Major finding: The 12-year disease-free survival (65.7 % vs 69.2%; hazard ratio [HR], 1.16; P = .50), overall survival (81.2 % vs 81.3%; HR, 1.17; P = .58), and posttreatment pregnancy (9 vs 4 patients; HR, 2.14; P = .20) were not significantly different in GnRHa+chemotherapy vs chemotherapy-only groups.

Study details: PROMISE-GIM6, a phase 3 superiority trial included 281 premenopausal women with hormone receptor-positive or -negative early BC who were randomly assigned to receive GnRHa+chemotherapy or chemotherapy alone.

Disclosures: This study was funded by IRCCS Ospedale Policlinico San Martino and Associazione Italiana per la Ricerca sul Cancro and the Italian Ministry of Health. Some of the authors declared serving as a consultant and/or receiving speaker honoraria and travel accommodation from various pharmaceutical companies.

Source: Lambertini M et al. J Natl Cancer Inst. 2021 Nov 25. doi: 10.1093/jnci/djab213.

Key clinical point: Final 12-year results from the PROMISE-GIM6 study reassures safety of concurrent administration of gonadotropin-releasing hormone agonist (GnRHa), triptorelin during chemotherapy in premenopausal women with early breast cancer (BC).

Major finding: The 12-year disease-free survival (65.7 % vs 69.2%; hazard ratio [HR], 1.16; P = .50), overall survival (81.2 % vs 81.3%; HR, 1.17; P = .58), and posttreatment pregnancy (9 vs 4 patients; HR, 2.14; P = .20) were not significantly different in GnRHa+chemotherapy vs chemotherapy-only groups.

Study details: PROMISE-GIM6, a phase 3 superiority trial included 281 premenopausal women with hormone receptor-positive or -negative early BC who were randomly assigned to receive GnRHa+chemotherapy or chemotherapy alone.

Disclosures: This study was funded by IRCCS Ospedale Policlinico San Martino and Associazione Italiana per la Ricerca sul Cancro and the Italian Ministry of Health. Some of the authors declared serving as a consultant and/or receiving speaker honoraria and travel accommodation from various pharmaceutical companies.

Source: Lambertini M et al. J Natl Cancer Inst. 2021 Nov 25. doi: 10.1093/jnci/djab213.

Key clinical point: Final 12-year results from the PROMISE-GIM6 study reassures safety of concurrent administration of gonadotropin-releasing hormone agonist (GnRHa), triptorelin during chemotherapy in premenopausal women with early breast cancer (BC).

Major finding: The 12-year disease-free survival (65.7 % vs 69.2%; hazard ratio [HR], 1.16; P = .50), overall survival (81.2 % vs 81.3%; HR, 1.17; P = .58), and posttreatment pregnancy (9 vs 4 patients; HR, 2.14; P = .20) were not significantly different in GnRHa+chemotherapy vs chemotherapy-only groups.

Study details: PROMISE-GIM6, a phase 3 superiority trial included 281 premenopausal women with hormone receptor-positive or -negative early BC who were randomly assigned to receive GnRHa+chemotherapy or chemotherapy alone.

Disclosures: This study was funded by IRCCS Ospedale Policlinico San Martino and Associazione Italiana per la Ricerca sul Cancro and the Italian Ministry of Health. Some of the authors declared serving as a consultant and/or receiving speaker honoraria and travel accommodation from various pharmaceutical companies.

Source: Lambertini M et al. J Natl Cancer Inst. 2021 Nov 25. doi: 10.1093/jnci/djab213.