Breast Cancer

Key clinical point: High or medium human trophoblast cell-surface antigen-2 (Trop-2) expression is associated with numerically higher survival with sacituzumab govitecan in patients with metastatic triple-negative breast cancer (TNBC).

Major finding: The median progression-free survival in the sacituzumab govitecan group was 6.9, 5.6, and 2.7 months in the patients with high, medium, and low Trop-2 H-scores, respectively. The median overall survival with sacituzumab govitecan was 14.2, 14.9, and 9.3 months in patients with high, medium, and low Trop-2 scores, respectively. The germline BRCA1/2 mutation status did not affect the outcomes in the sacituzumab govitecan vs. chemotherapy group.

Study details: A prespecified, exploratory biomarker analysis from the ASCENT trial evaluated the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes in patients with metastatic TNBC. The patients were randomly assigned to sacituzumab govitecan or chemotherapy.

Disclosures: This study was sponsored by Immunomedics, Inc. The authors received consulting/advisory fees, research funding, travel/accommodations/expenses, speaker fees, nonfinancial support, and/or declared intellectual property rights, patents, and royalties from various companies/organizations. Dr. K Kalinsky reported spouse employment at Array Biopharma. The authors disclosed no other potential conflicts of interest.

Source: Bardia A et al. Ann Oncol. 2021 Jun 8. doi: 10.1016/j.annonc.2021.06.002.

Key clinical point: High or medium human trophoblast cell-surface antigen-2 (Trop-2) expression is associated with numerically higher survival with sacituzumab govitecan in patients with metastatic triple-negative breast cancer (TNBC).

Major finding: The median progression-free survival in the sacituzumab govitecan group was 6.9, 5.6, and 2.7 months in the patients with high, medium, and low Trop-2 H-scores, respectively. The median overall survival with sacituzumab govitecan was 14.2, 14.9, and 9.3 months in patients with high, medium, and low Trop-2 scores, respectively. The germline BRCA1/2 mutation status did not affect the outcomes in the sacituzumab govitecan vs. chemotherapy group.

Study details: A prespecified, exploratory biomarker analysis from the ASCENT trial evaluated the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes in patients with metastatic TNBC. The patients were randomly assigned to sacituzumab govitecan or chemotherapy.

Disclosures: This study was sponsored by Immunomedics, Inc. The authors received consulting/advisory fees, research funding, travel/accommodations/expenses, speaker fees, nonfinancial support, and/or declared intellectual property rights, patents, and royalties from various companies/organizations. Dr. K Kalinsky reported spouse employment at Array Biopharma. The authors disclosed no other potential conflicts of interest.

Source: Bardia A et al. Ann Oncol. 2021 Jun 8. doi: 10.1016/j.annonc.2021.06.002.

Key clinical point: High or medium human trophoblast cell-surface antigen-2 (Trop-2) expression is associated with numerically higher survival with sacituzumab govitecan in patients with metastatic triple-negative breast cancer (TNBC).

Major finding: The median progression-free survival in the sacituzumab govitecan group was 6.9, 5.6, and 2.7 months in the patients with high, medium, and low Trop-2 H-scores, respectively. The median overall survival with sacituzumab govitecan was 14.2, 14.9, and 9.3 months in patients with high, medium, and low Trop-2 scores, respectively. The germline BRCA1/2 mutation status did not affect the outcomes in the sacituzumab govitecan vs. chemotherapy group.

Study details: A prespecified, exploratory biomarker analysis from the ASCENT trial evaluated the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes in patients with metastatic TNBC. The patients were randomly assigned to sacituzumab govitecan or chemotherapy.

Disclosures: This study was sponsored by Immunomedics, Inc. The authors received consulting/advisory fees, research funding, travel/accommodations/expenses, speaker fees, nonfinancial support, and/or declared intellectual property rights, patents, and royalties from various companies/organizations. Dr. K Kalinsky reported spouse employment at Array Biopharma. The authors disclosed no other potential conflicts of interest.

Source: Bardia A et al. Ann Oncol. 2021 Jun 8. doi: 10.1016/j.annonc.2021.06.002.

Key clinical point: Olaparib monotherapy is effective in germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer in a real-world setting.

Major finding: The median progression-free survival was 8.11 months, and the clinical response rate was 48.6%. The grade 3 or higher treatment-related adverse event rate was 25.4%. There were no new safety signals.

Study details: An interim analysis of an open-label, single-arm, phase 3b LUCY trial including 252 previously treated patients with HER2-negative metastatic breast cancer with a germline BRCA mutation who received olaparib.

Disclosures: The study was funded by AstraZeneca. Dr. S McCutcheon was an employee and stockholder of AstraZeneca LP. Dr. J Bennett and Dr. G Walker were contractors for AstraZeneca LP. The authors received consulting/speaker fees or research support from various sources.

Source: Gelmon KA et al. Eur J Cancer. 2021 Jun 1. doi: 10.1016/j.ejca.2021.03.029.

Key clinical point: Olaparib monotherapy is effective in germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer in a real-world setting.

Major finding: The median progression-free survival was 8.11 months, and the clinical response rate was 48.6%. The grade 3 or higher treatment-related adverse event rate was 25.4%. There were no new safety signals.

Study details: An interim analysis of an open-label, single-arm, phase 3b LUCY trial including 252 previously treated patients with HER2-negative metastatic breast cancer with a germline BRCA mutation who received olaparib.

Disclosures: The study was funded by AstraZeneca. Dr. S McCutcheon was an employee and stockholder of AstraZeneca LP. Dr. J Bennett and Dr. G Walker were contractors for AstraZeneca LP. The authors received consulting/speaker fees or research support from various sources.

Source: Gelmon KA et al. Eur J Cancer. 2021 Jun 1. doi: 10.1016/j.ejca.2021.03.029.

Key clinical point: Olaparib monotherapy is effective in germline BRCA-mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer in a real-world setting.

Major finding: The median progression-free survival was 8.11 months, and the clinical response rate was 48.6%. The grade 3 or higher treatment-related adverse event rate was 25.4%. There were no new safety signals.

Study details: An interim analysis of an open-label, single-arm, phase 3b LUCY trial including 252 previously treated patients with HER2-negative metastatic breast cancer with a germline BRCA mutation who received olaparib.

Disclosures: The study was funded by AstraZeneca. Dr. S McCutcheon was an employee and stockholder of AstraZeneca LP. Dr. J Bennett and Dr. G Walker were contractors for AstraZeneca LP. The authors received consulting/speaker fees or research support from various sources.

Source: Gelmon KA et al. Eur J Cancer. 2021 Jun 1. doi: 10.1016/j.ejca.2021.03.029.

Key clinical point: The Internet–based-targeted psychological interventions fail to reduce fear of recurrence among early breast cancer survivors.

Major finding: The Fear of Cancer Recurrence Inventory (FCRI) scores significantly decreased at 8 weeks from baseline in all groups (P less than .001). The magnitude of reduction in FCRI scores was similar in cognitive-behavioral interventions and attention controls.

Study details: The randomized controlled FoRtitude study of breast cancer survivors who completed primary treatment. The survivors were randomly assigned to 4 Internet-based interventions or controls. The 4 interventions given for 4 weeks consisted of 3 cognitive behavioral interventions (relaxation, cognitive restructuring, and worry practice vs. attention controls) and telecoaching (motivational interviewing to improve adherence vs. no telecoaching).

Disclosures: This work was supported by the National Cancer Institute at the National Institutes of Health and the ECOG-ACRIN Medical Research Foundation. The authors did not disclose any conflict of interest.

Source: Wagner LI. J Natl Cancer Inst. 2021 May 31. doi: 10.1093/jnci/djab100.

Key clinical point: The Internet–based-targeted psychological interventions fail to reduce fear of recurrence among early breast cancer survivors.

Major finding: The Fear of Cancer Recurrence Inventory (FCRI) scores significantly decreased at 8 weeks from baseline in all groups (P less than .001). The magnitude of reduction in FCRI scores was similar in cognitive-behavioral interventions and attention controls.

Study details: The randomized controlled FoRtitude study of breast cancer survivors who completed primary treatment. The survivors were randomly assigned to 4 Internet-based interventions or controls. The 4 interventions given for 4 weeks consisted of 3 cognitive behavioral interventions (relaxation, cognitive restructuring, and worry practice vs. attention controls) and telecoaching (motivational interviewing to improve adherence vs. no telecoaching).

Disclosures: This work was supported by the National Cancer Institute at the National Institutes of Health and the ECOG-ACRIN Medical Research Foundation. The authors did not disclose any conflict of interest.

Source: Wagner LI. J Natl Cancer Inst. 2021 May 31. doi: 10.1093/jnci/djab100.

Key clinical point: The Internet–based-targeted psychological interventions fail to reduce fear of recurrence among early breast cancer survivors.

Major finding: The Fear of Cancer Recurrence Inventory (FCRI) scores significantly decreased at 8 weeks from baseline in all groups (P less than .001). The magnitude of reduction in FCRI scores was similar in cognitive-behavioral interventions and attention controls.

Study details: The randomized controlled FoRtitude study of breast cancer survivors who completed primary treatment. The survivors were randomly assigned to 4 Internet-based interventions or controls. The 4 interventions given for 4 weeks consisted of 3 cognitive behavioral interventions (relaxation, cognitive restructuring, and worry practice vs. attention controls) and telecoaching (motivational interviewing to improve adherence vs. no telecoaching).

Disclosures: This work was supported by the National Cancer Institute at the National Institutes of Health and the ECOG-ACRIN Medical Research Foundation. The authors did not disclose any conflict of interest.

Source: Wagner LI. J Natl Cancer Inst. 2021 May 31. doi: 10.1093/jnci/djab100.

Key clinical point: The survival among patients with metastatic breast cancer has improved over past 3 decades.

Major finding: During 1988-2015, 1-year overall survival (OS) rate increased from 62.3% to 72.4% and 1-year cancer-specific survival (CSS) rate increased from 64.7% to 74.1%. Similarly, 5-year OS rate increased from 19.4% to 24.3% and 5-year CSS rate increased from 23.4% to 28.0% during 1998-2011.

Study details: A retrospective cohort study of 47,034 patients with de novo metastatic breast cancer in the Surveillance, Epidemiology, and End Results database from 1988 to 2016.

Disclosures: This study is in part supported by Duke Cancer Institute. Dr. OM Fayanju is supported by the National Institutes of Health. Some of the authors received research funding and consulting/advisory fees from various sources. Dr. JK Plichta and Dr. ES Hwang have served on various Cancer Committees. The other authors reported no competing interests.

Source: Taskindoust M. Ann Surg Oncol. 2021 May 28. doi: 10.1245/s10434-021-10227-3.

Key clinical point: The survival among patients with metastatic breast cancer has improved over past 3 decades.

Major finding: During 1988-2015, 1-year overall survival (OS) rate increased from 62.3% to 72.4% and 1-year cancer-specific survival (CSS) rate increased from 64.7% to 74.1%. Similarly, 5-year OS rate increased from 19.4% to 24.3% and 5-year CSS rate increased from 23.4% to 28.0% during 1998-2011.

Study details: A retrospective cohort study of 47,034 patients with de novo metastatic breast cancer in the Surveillance, Epidemiology, and End Results database from 1988 to 2016.

Disclosures: This study is in part supported by Duke Cancer Institute. Dr. OM Fayanju is supported by the National Institutes of Health. Some of the authors received research funding and consulting/advisory fees from various sources. Dr. JK Plichta and Dr. ES Hwang have served on various Cancer Committees. The other authors reported no competing interests.

Source: Taskindoust M. Ann Surg Oncol. 2021 May 28. doi: 10.1245/s10434-021-10227-3.

Key clinical point: The survival among patients with metastatic breast cancer has improved over past 3 decades.

Major finding: During 1988-2015, 1-year overall survival (OS) rate increased from 62.3% to 72.4% and 1-year cancer-specific survival (CSS) rate increased from 64.7% to 74.1%. Similarly, 5-year OS rate increased from 19.4% to 24.3% and 5-year CSS rate increased from 23.4% to 28.0% during 1998-2011.

Study details: A retrospective cohort study of 47,034 patients with de novo metastatic breast cancer in the Surveillance, Epidemiology, and End Results database from 1988 to 2016.

Disclosures: This study is in part supported by Duke Cancer Institute. Dr. OM Fayanju is supported by the National Institutes of Health. Some of the authors received research funding and consulting/advisory fees from various sources. Dr. JK Plichta and Dr. ES Hwang have served on various Cancer Committees. The other authors reported no competing interests.

Source: Taskindoust M. Ann Surg Oncol. 2021 May 28. doi: 10.1245/s10434-021-10227-3.

Key clinical point: In patients with triple-negative breast cancer (TNBC), the risk for locoregional recurrence and distant metastasis is lower when treated with breast-conserving surgery (BCS) vs. mastectomy.

Major finding: BCS vs. mastectomy was associated with lower risk for locoregional recurrence (unadjusted pooled odds ratio, 0.64; P = .002). The risk for distant metastasis was also significantly lower with BCS vs. mastectomy (unadjusted pooled odds ratio, 0.70; P = .02).

Study details: A meta-analysis of 14 studies including 19,819 patients with TNBC who underwent either BCS or mastectomy.

Disclosures: This meta-analysis was supported by investigator grants from the National Health and Medical Research Council and the National Breast Cancer Foundation. The authors declared no conflicts of interest.

Source: Fancellu A. Br J Surg. 2021 May 31. doi: 10.1093/bjs/znab145.

Key clinical point: In patients with triple-negative breast cancer (TNBC), the risk for locoregional recurrence and distant metastasis is lower when treated with breast-conserving surgery (BCS) vs. mastectomy.

Major finding: BCS vs. mastectomy was associated with lower risk for locoregional recurrence (unadjusted pooled odds ratio, 0.64; P = .002). The risk for distant metastasis was also significantly lower with BCS vs. mastectomy (unadjusted pooled odds ratio, 0.70; P = .02).

Study details: A meta-analysis of 14 studies including 19,819 patients with TNBC who underwent either BCS or mastectomy.

Disclosures: This meta-analysis was supported by investigator grants from the National Health and Medical Research Council and the National Breast Cancer Foundation. The authors declared no conflicts of interest.

Source: Fancellu A. Br J Surg. 2021 May 31. doi: 10.1093/bjs/znab145.

Key clinical point: In patients with triple-negative breast cancer (TNBC), the risk for locoregional recurrence and distant metastasis is lower when treated with breast-conserving surgery (BCS) vs. mastectomy.

Major finding: BCS vs. mastectomy was associated with lower risk for locoregional recurrence (unadjusted pooled odds ratio, 0.64; P = .002). The risk for distant metastasis was also significantly lower with BCS vs. mastectomy (unadjusted pooled odds ratio, 0.70; P = .02).

Study details: A meta-analysis of 14 studies including 19,819 patients with TNBC who underwent either BCS or mastectomy.

Disclosures: This meta-analysis was supported by investigator grants from the National Health and Medical Research Council and the National Breast Cancer Foundation. The authors declared no conflicts of interest.

Source: Fancellu A. Br J Surg. 2021 May 31. doi: 10.1093/bjs/znab145.

Key clinical point: Patients with hormone receptor (HR)-positive breast cancer derive survival benefit from treatment with predominantly aromatase inhibitors after chemotherapy.

Major finding: The recurrence-free survival significantly improved in patients who received aromatase inhibitor for greater than 75% of their endocrine treatment duration (adjusted hazard ratio [aHR], 0.63; 95% confidence interval [CI], 0.46-0.86) and overall survival (aHR, 0.50; 95% CI, 0.34-0.74) vs. those who received aromatase inhibitors for less than 25% of their endocrine treatment duration.

Study details: A population-based cohort study of patients with stage I-III, HR-positive invasive breast cancer diagnosed between 2004 and 2007 and received adjuvant chemotherapy and endocrine treatment.

Disclosures: This work was funded by the Netherlands Organization for Health Research and Development, A Sisters Hope, and De Vrienden van UMC Utrecht. Some authors reported research support, grants, advisory fees, and nonfinancial support from various sources outside this work.

Source: Dackus GM et al. J Natl Cancer Inst. 2021 Jun 8. doi: 10.1093/jnci/djab091.

Key clinical point: Patients with hormone receptor (HR)-positive breast cancer derive survival benefit from treatment with predominantly aromatase inhibitors after chemotherapy.

Major finding: The recurrence-free survival significantly improved in patients who received aromatase inhibitor for greater than 75% of their endocrine treatment duration (adjusted hazard ratio [aHR], 0.63; 95% confidence interval [CI], 0.46-0.86) and overall survival (aHR, 0.50; 95% CI, 0.34-0.74) vs. those who received aromatase inhibitors for less than 25% of their endocrine treatment duration.

Study details: A population-based cohort study of patients with stage I-III, HR-positive invasive breast cancer diagnosed between 2004 and 2007 and received adjuvant chemotherapy and endocrine treatment.

Disclosures: This work was funded by the Netherlands Organization for Health Research and Development, A Sisters Hope, and De Vrienden van UMC Utrecht. Some authors reported research support, grants, advisory fees, and nonfinancial support from various sources outside this work.

Source: Dackus GM et al. J Natl Cancer Inst. 2021 Jun 8. doi: 10.1093/jnci/djab091.

Key clinical point: Patients with hormone receptor (HR)-positive breast cancer derive survival benefit from treatment with predominantly aromatase inhibitors after chemotherapy.

Major finding: The recurrence-free survival significantly improved in patients who received aromatase inhibitor for greater than 75% of their endocrine treatment duration (adjusted hazard ratio [aHR], 0.63; 95% confidence interval [CI], 0.46-0.86) and overall survival (aHR, 0.50; 95% CI, 0.34-0.74) vs. those who received aromatase inhibitors for less than 25% of their endocrine treatment duration.

Study details: A population-based cohort study of patients with stage I-III, HR-positive invasive breast cancer diagnosed between 2004 and 2007 and received adjuvant chemotherapy and endocrine treatment.

Disclosures: This work was funded by the Netherlands Organization for Health Research and Development, A Sisters Hope, and De Vrienden van UMC Utrecht. Some authors reported research support, grants, advisory fees, and nonfinancial support from various sources outside this work.

Source: Dackus GM et al. J Natl Cancer Inst. 2021 Jun 8. doi: 10.1093/jnci/djab091.

Key clinical point: In patients with hormone receptor (HR)-positive, human epidermal growth receptor (HER)-negative advanced breast cancer, the addition of ribociclib to fulvestrant extends median overall survival by 12 months.

Major finding: The median overall survival was 53.7 months with ribociclib and 41.5 months with placebo (hazard ratio, 0.73; 95% confidence interval, 0.59-0.90 months) at a median follow-up of 56.3 months. Neutropenia was the most common grade 3-4 adverse event.

Study details: A phase 3, randomized, double-blind, placebo-controlled MONALEESA-3 trial including 726 chemotherapy-naïve patients (men and postmenopausal women) with HR-positive, HER2-negative advanced breast cancer randomly assigned 2:1 to receive fulvestrant with either ribociclib or placebo.

Disclosures: The study was funded by the Novartis Pharmaceuticals Corporation. The authors reported advisory/consulting fees, stock ownership, research funding, grants, personal fees, honoraria, travel expenses, and nonfinancial support from various sources outside this work.

Source: Slamon DJ et al. Ann Oncol. 2021 Jun 5. doi: 10.1016/j.annonc.2021.05.353.

Key clinical point: In patients with hormone receptor (HR)-positive, human epidermal growth receptor (HER)-negative advanced breast cancer, the addition of ribociclib to fulvestrant extends median overall survival by 12 months.

Major finding: The median overall survival was 53.7 months with ribociclib and 41.5 months with placebo (hazard ratio, 0.73; 95% confidence interval, 0.59-0.90 months) at a median follow-up of 56.3 months. Neutropenia was the most common grade 3-4 adverse event.

Study details: A phase 3, randomized, double-blind, placebo-controlled MONALEESA-3 trial including 726 chemotherapy-naïve patients (men and postmenopausal women) with HR-positive, HER2-negative advanced breast cancer randomly assigned 2:1 to receive fulvestrant with either ribociclib or placebo.

Disclosures: The study was funded by the Novartis Pharmaceuticals Corporation. The authors reported advisory/consulting fees, stock ownership, research funding, grants, personal fees, honoraria, travel expenses, and nonfinancial support from various sources outside this work.

Source: Slamon DJ et al. Ann Oncol. 2021 Jun 5. doi: 10.1016/j.annonc.2021.05.353.

Key clinical point: In patients with hormone receptor (HR)-positive, human epidermal growth receptor (HER)-negative advanced breast cancer, the addition of ribociclib to fulvestrant extends median overall survival by 12 months.

Major finding: The median overall survival was 53.7 months with ribociclib and 41.5 months with placebo (hazard ratio, 0.73; 95% confidence interval, 0.59-0.90 months) at a median follow-up of 56.3 months. Neutropenia was the most common grade 3-4 adverse event.

Study details: A phase 3, randomized, double-blind, placebo-controlled MONALEESA-3 trial including 726 chemotherapy-naïve patients (men and postmenopausal women) with HR-positive, HER2-negative advanced breast cancer randomly assigned 2:1 to receive fulvestrant with either ribociclib or placebo.

Disclosures: The study was funded by the Novartis Pharmaceuticals Corporation. The authors reported advisory/consulting fees, stock ownership, research funding, grants, personal fees, honoraria, travel expenses, and nonfinancial support from various sources outside this work.

Source: Slamon DJ et al. Ann Oncol. 2021 Jun 5. doi: 10.1016/j.annonc.2021.05.353.

Key clinical point: Platinum agents do not improve outcomes in patients with basal subtype triple-negative breast cancer (TNBC) and residual invasive disease post-neoadjuvant chemotherapy (NAC) and are associated with higher toxicity rate vs. capecitabine.

Major finding: The invasive disease-free survival was not significantly different between platinum and capecitabine groups (hazard ratio, 1.06; 95% confidence interval, 0.62-1.81) after a median follow-up of 20 months. Grade 3 and 4 toxicities were more frequent in the platinum vs. capecitabine group (26% vs. 15%).

Study details: A phase 3, randomized controlled EA1131 trial involving 415 patients with stage II-III TNBC post-NAC, randomly assigned to receive platinum-based chemotherapy or capecitabine.

Disclosures: This study was supported by the National Cancer Institute of the National Institutes of Health. The authors received consulting/advisory fees, research funding, honoraria, travel/accommodation/expenses, and reported stock and other ownership interests in various companies. Some authors also reported patents, royalties, and other intellectual property.

Source: Mayer IA et al. J Clin Oncol. 2021 Jun 6. doi: 10.1200/JCO.21.00976.

Key clinical point: Platinum agents do not improve outcomes in patients with basal subtype triple-negative breast cancer (TNBC) and residual invasive disease post-neoadjuvant chemotherapy (NAC) and are associated with higher toxicity rate vs. capecitabine.

Major finding: The invasive disease-free survival was not significantly different between platinum and capecitabine groups (hazard ratio, 1.06; 95% confidence interval, 0.62-1.81) after a median follow-up of 20 months. Grade 3 and 4 toxicities were more frequent in the platinum vs. capecitabine group (26% vs. 15%).

Study details: A phase 3, randomized controlled EA1131 trial involving 415 patients with stage II-III TNBC post-NAC, randomly assigned to receive platinum-based chemotherapy or capecitabine.

Disclosures: This study was supported by the National Cancer Institute of the National Institutes of Health. The authors received consulting/advisory fees, research funding, honoraria, travel/accommodation/expenses, and reported stock and other ownership interests in various companies. Some authors also reported patents, royalties, and other intellectual property.

Source: Mayer IA et al. J Clin Oncol. 2021 Jun 6. doi: 10.1200/JCO.21.00976.

Key clinical point: Platinum agents do not improve outcomes in patients with basal subtype triple-negative breast cancer (TNBC) and residual invasive disease post-neoadjuvant chemotherapy (NAC) and are associated with higher toxicity rate vs. capecitabine.

Major finding: The invasive disease-free survival was not significantly different between platinum and capecitabine groups (hazard ratio, 1.06; 95% confidence interval, 0.62-1.81) after a median follow-up of 20 months. Grade 3 and 4 toxicities were more frequent in the platinum vs. capecitabine group (26% vs. 15%).

Study details: A phase 3, randomized controlled EA1131 trial involving 415 patients with stage II-III TNBC post-NAC, randomly assigned to receive platinum-based chemotherapy or capecitabine.

Disclosures: This study was supported by the National Cancer Institute of the National Institutes of Health. The authors received consulting/advisory fees, research funding, honoraria, travel/accommodation/expenses, and reported stock and other ownership interests in various companies. Some authors also reported patents, royalties, and other intellectual property.

Source: Mayer IA et al. J Clin Oncol. 2021 Jun 6. doi: 10.1200/JCO.21.00976.

Key clinical point: Adjuvant olaparib prolongs invasive disease-free survival and distant disease-free survival in patients with high-risk BRCA1/2-mutated human epidermal growth factor 2 (HER2)-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy.

Major finding: Adjuvant olaparib significantly improved invasive disease-free survival (hazard ratio, 0.58; P less than .001) and distant disease-free survival (hazard ratio, 0.57; P less than .001). The serious adverse event rate was 8.7% in the olaparib group and 8.4% in the placebo group.

Study details: A phase 3 double-blind, randomized OlympiA trial evaluated 1,836 patients with high-risk BRCA1/2-mutated HER2-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy. Patients were randomly assigned to olaparib or placebo.

Disclosures: The study received funding from the National Cancer Institute and AstraZeneca. The authors reported receiving grants, honoraria, advisory/speaker/consulting fees, financial/nonfinancial support, and travel expense from various sources and/or owning stocks in pharmaceutical companies. Dr. SJ Hollingsworth, Dr. A Fielding, and Dr. N Baker were employees at AstraZeneca.

Source: Tutt ANJ et al. New Eng J Med. 2021 Jun 3. doi: 10.1056/NEJMoa2105215.

Key clinical point: Adjuvant olaparib prolongs invasive disease-free survival and distant disease-free survival in patients with high-risk BRCA1/2-mutated human epidermal growth factor 2 (HER2)-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy.

Major finding: Adjuvant olaparib significantly improved invasive disease-free survival (hazard ratio, 0.58; P less than .001) and distant disease-free survival (hazard ratio, 0.57; P less than .001). The serious adverse event rate was 8.7% in the olaparib group and 8.4% in the placebo group.

Study details: A phase 3 double-blind, randomized OlympiA trial evaluated 1,836 patients with high-risk BRCA1/2-mutated HER2-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy. Patients were randomly assigned to olaparib or placebo.

Disclosures: The study received funding from the National Cancer Institute and AstraZeneca. The authors reported receiving grants, honoraria, advisory/speaker/consulting fees, financial/nonfinancial support, and travel expense from various sources and/or owning stocks in pharmaceutical companies. Dr. SJ Hollingsworth, Dr. A Fielding, and Dr. N Baker were employees at AstraZeneca.

Source: Tutt ANJ et al. New Eng J Med. 2021 Jun 3. doi: 10.1056/NEJMoa2105215.

Key clinical point: Adjuvant olaparib prolongs invasive disease-free survival and distant disease-free survival in patients with high-risk BRCA1/2-mutated human epidermal growth factor 2 (HER2)-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy.

Major finding: Adjuvant olaparib significantly improved invasive disease-free survival (hazard ratio, 0.58; P less than .001) and distant disease-free survival (hazard ratio, 0.57; P less than .001). The serious adverse event rate was 8.7% in the olaparib group and 8.4% in the placebo group.

Study details: A phase 3 double-blind, randomized OlympiA trial evaluated 1,836 patients with high-risk BRCA1/2-mutated HER2-negative early breast cancer who received local treatment and adjuvant/neoadjuvant chemotherapy. Patients were randomly assigned to olaparib or placebo.

Disclosures: The study received funding from the National Cancer Institute and AstraZeneca. The authors reported receiving grants, honoraria, advisory/speaker/consulting fees, financial/nonfinancial support, and travel expense from various sources and/or owning stocks in pharmaceutical companies. Dr. SJ Hollingsworth, Dr. A Fielding, and Dr. N Baker were employees at AstraZeneca.

Source: Tutt ANJ et al. New Eng J Med. 2021 Jun 3. doi: 10.1056/NEJMoa2105215.

The role of adjuvant olaparib was investigated in the phase 3 OlympiA trial, which included 1,836 patients with high-risk HER2-negative gBRCAm early breast cancer who received local treatment and adjuvant or neoadjuvant chemotherapy. One year of adjuvant olaparib was associated with a significant improvement in invasive disease-free survival (hazard ratio [HR] 0.58, P < .001) and distant disease-free survival (HR 0.57, P < .001). The 3-year invasive disease-free survival (iDFS) was 85.9% in the olaparib group and 77.1% in the placebo group (absolute benefit of 8.8%), and 3-year distant disease-free survival (dDFS) was 87.5% and 80.4%, respectively (difference of 7.1%). These results are considered practice changing and lead to questions regarding the expansion of germline testing in early stage breast cancer. Furthermore, PARP inhibitors have shown exciting results in the neoadjuvant setting. Among 61 patients with gBRCAm HER2-negative early breast cancer, neoadjuvant talazoparib produced a pathologic complete response (pCR) in 49.2%, and there may be a subgroup of patients for whom this approach is relevant.

The presence of residual disease after neoadjuvant chemotherapy has prognostic implications and can help tailor adjuvant treatment recommendations. The CREATE-X trial has established the role of adjuvant capecitabine for patients with triple-negative breast cancer with residual disease after pre-operative chemotherapy. The phase 3 EA1131 trial randomized 415 patients with stage II-III triple-negative breast cancer and residual disease post-neoadjuvant chemotherapy to platinum agent or capecitabine. There was no significant difference in 3-year iDFS (42% for platinum vs 49% for capecitabine; HR 1.06, 95% CI 0.62-1.81), and higher hematologic toxicity and dose reductions in the platinum arm. These data support the continued use of capecitabine in this population, and the high event rate highlights the need for more effective therapies in this setting.

The majority of patients with HR+/HER2- MBC will receive a CDK 4/6 inhibitor at some point during their treatment course. In an updated analysis of the phase 3 MONALEESA-3 trial which included postmenopausal patients with HR+HER2- MBC, with median follow-up of 56.3 months, ribociclib plus fulvestrant continued to show an overall survival (OS) benefit of greater than 1 year compared with fulvestrant alone (median OS 53.7 months vs 41.5 months in the ribociclib vs placebo arm, respectively; HR 0.726, 95% CI 0.59-0.90). Additionally, extended follow-up of the PALOMA-3 trial demonstrated OS benefit with palbociclib plus fulvestrant compared to fulvestrant alone in patients with HR+/HER2- MBC; at median follow-up of 73.3 months, median OS was 34.8 months in the palbociclib arm vs 28.0 months in the placebo arm (HR 0.81, P = .0221). Sequencing of other targeted therapies (such as PI3K inhibitors), predictors of CDK 4/6 inhibitor response in different intrinsic subtypes, and the role of CDK 4/6 inhibitor use beyond progression are areas where further research is warranted.

References:

Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017;377(6):523-533.

Litton JK, Beck JT, Jones JM, et al. Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. J Clin Oncol 39, 2021 (suppl 15; abstr 505).

Symmans WF, Wei C, Gould R, et al. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. J Clin Oncol. 2017;35:1049-1060.

Masuda N, Lee SJ, Ohtani S, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376:2147-2159.

Cristofanilli M, Rugo H, Im SA, et al. Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3. J Clin Oncol. 2021; 39:15_suppl, 1000-1000.

The role of adjuvant olaparib was investigated in the phase 3 OlympiA trial, which included 1,836 patients with high-risk HER2-negative gBRCAm early breast cancer who received local treatment and adjuvant or neoadjuvant chemotherapy. One year of adjuvant olaparib was associated with a significant improvement in invasive disease-free survival (hazard ratio [HR] 0.58, P < .001) and distant disease-free survival (HR 0.57, P < .001). The 3-year invasive disease-free survival (iDFS) was 85.9% in the olaparib group and 77.1% in the placebo group (absolute benefit of 8.8%), and 3-year distant disease-free survival (dDFS) was 87.5% and 80.4%, respectively (difference of 7.1%). These results are considered practice changing and lead to questions regarding the expansion of germline testing in early stage breast cancer. Furthermore, PARP inhibitors have shown exciting results in the neoadjuvant setting. Among 61 patients with gBRCAm HER2-negative early breast cancer, neoadjuvant talazoparib produced a pathologic complete response (pCR) in 49.2%, and there may be a subgroup of patients for whom this approach is relevant.

The presence of residual disease after neoadjuvant chemotherapy has prognostic implications and can help tailor adjuvant treatment recommendations. The CREATE-X trial has established the role of adjuvant capecitabine for patients with triple-negative breast cancer with residual disease after pre-operative chemotherapy. The phase 3 EA1131 trial randomized 415 patients with stage II-III triple-negative breast cancer and residual disease post-neoadjuvant chemotherapy to platinum agent or capecitabine. There was no significant difference in 3-year iDFS (42% for platinum vs 49% for capecitabine; HR 1.06, 95% CI 0.62-1.81), and higher hematologic toxicity and dose reductions in the platinum arm. These data support the continued use of capecitabine in this population, and the high event rate highlights the need for more effective therapies in this setting.

The majority of patients with HR+/HER2- MBC will receive a CDK 4/6 inhibitor at some point during their treatment course. In an updated analysis of the phase 3 MONALEESA-3 trial which included postmenopausal patients with HR+HER2- MBC, with median follow-up of 56.3 months, ribociclib plus fulvestrant continued to show an overall survival (OS) benefit of greater than 1 year compared with fulvestrant alone (median OS 53.7 months vs 41.5 months in the ribociclib vs placebo arm, respectively; HR 0.726, 95% CI 0.59-0.90). Additionally, extended follow-up of the PALOMA-3 trial demonstrated OS benefit with palbociclib plus fulvestrant compared to fulvestrant alone in patients with HR+/HER2- MBC; at median follow-up of 73.3 months, median OS was 34.8 months in the palbociclib arm vs 28.0 months in the placebo arm (HR 0.81, P = .0221). Sequencing of other targeted therapies (such as PI3K inhibitors), predictors of CDK 4/6 inhibitor response in different intrinsic subtypes, and the role of CDK 4/6 inhibitor use beyond progression are areas where further research is warranted.

References:

Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017;377(6):523-533.

Litton JK, Beck JT, Jones JM, et al. Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. J Clin Oncol 39, 2021 (suppl 15; abstr 505).

Symmans WF, Wei C, Gould R, et al. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. J Clin Oncol. 2017;35:1049-1060.

Masuda N, Lee SJ, Ohtani S, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376:2147-2159.

Cristofanilli M, Rugo H, Im SA, et al. Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3. J Clin Oncol. 2021; 39:15_suppl, 1000-1000.

The role of adjuvant olaparib was investigated in the phase 3 OlympiA trial, which included 1,836 patients with high-risk HER2-negative gBRCAm early breast cancer who received local treatment and adjuvant or neoadjuvant chemotherapy. One year of adjuvant olaparib was associated with a significant improvement in invasive disease-free survival (hazard ratio [HR] 0.58, P < .001) and distant disease-free survival (HR 0.57, P < .001). The 3-year invasive disease-free survival (iDFS) was 85.9% in the olaparib group and 77.1% in the placebo group (absolute benefit of 8.8%), and 3-year distant disease-free survival (dDFS) was 87.5% and 80.4%, respectively (difference of 7.1%). These results are considered practice changing and lead to questions regarding the expansion of germline testing in early stage breast cancer. Furthermore, PARP inhibitors have shown exciting results in the neoadjuvant setting. Among 61 patients with gBRCAm HER2-negative early breast cancer, neoadjuvant talazoparib produced a pathologic complete response (pCR) in 49.2%, and there may be a subgroup of patients for whom this approach is relevant.

The presence of residual disease after neoadjuvant chemotherapy has prognostic implications and can help tailor adjuvant treatment recommendations. The CREATE-X trial has established the role of adjuvant capecitabine for patients with triple-negative breast cancer with residual disease after pre-operative chemotherapy. The phase 3 EA1131 trial randomized 415 patients with stage II-III triple-negative breast cancer and residual disease post-neoadjuvant chemotherapy to platinum agent or capecitabine. There was no significant difference in 3-year iDFS (42% for platinum vs 49% for capecitabine; HR 1.06, 95% CI 0.62-1.81), and higher hematologic toxicity and dose reductions in the platinum arm. These data support the continued use of capecitabine in this population, and the high event rate highlights the need for more effective therapies in this setting.

The majority of patients with HR+/HER2- MBC will receive a CDK 4/6 inhibitor at some point during their treatment course. In an updated analysis of the phase 3 MONALEESA-3 trial which included postmenopausal patients with HR+HER2- MBC, with median follow-up of 56.3 months, ribociclib plus fulvestrant continued to show an overall survival (OS) benefit of greater than 1 year compared with fulvestrant alone (median OS 53.7 months vs 41.5 months in the ribociclib vs placebo arm, respectively; HR 0.726, 95% CI 0.59-0.90). Additionally, extended follow-up of the PALOMA-3 trial demonstrated OS benefit with palbociclib plus fulvestrant compared to fulvestrant alone in patients with HR+/HER2- MBC; at median follow-up of 73.3 months, median OS was 34.8 months in the palbociclib arm vs 28.0 months in the placebo arm (HR 0.81, P = .0221). Sequencing of other targeted therapies (such as PI3K inhibitors), predictors of CDK 4/6 inhibitor response in different intrinsic subtypes, and the role of CDK 4/6 inhibitor use beyond progression are areas where further research is warranted.

References:

Robson M, Im SA, Senkus E, et al. Olaparib for Metastatic Breast Cancer in Patients with a Germline BRCA Mutation. N Engl J Med. 2017;377(6):523-533.

Litton JK, Beck JT, Jones JM, et al. Neoadjuvant talazoparib in patients with germline BRCA1/2 (gBRCA1/2) mutation-positive, early HER2-negative breast cancer (BC): Results of a phase 2 study. J Clin Oncol 39, 2021 (suppl 15; abstr 505).

Symmans WF, Wei C, Gould R, et al. Long-Term Prognostic Risk After Neoadjuvant Chemotherapy Associated With Residual Cancer Burden and Breast Cancer Subtype. J Clin Oncol. 2017;35:1049-1060.

Masuda N, Lee SJ, Ohtani S, et al. Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy. N Engl J Med. 2017;376:2147-2159.

Cristofanilli M, Rugo H, Im SA, et al. Overall survival (OS) with palbociclib (PAL) + fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3. J Clin Oncol. 2021; 39:15_suppl, 1000-1000.