Efficacy and safety in older patient subsets in studies of endocrine monotherapy versus combination therapy in patients with HR+/HER2− advanced breast cancer: a review
Prospective information regarding the tolerability and efficacy of endocrine therapy (ET) alone and in combination with targeted agents in older patients in the metastatic setting is limited. This review summarizes available trial data in this population.
We searched PubMed for Phase 2 or 3 trials with age-stratified patient cohorts (≥ 65 vs. < 65 years in most studies) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer treated with ET ± targeted agents.
We identified 19 studies reporting 10 clinical trials. Efficacy was similar in age-stratified subsets. There was a reduced disease progression risk for ET + everolimus, palbociclib, or ribociclib versus ET alone. In the first-line setting, median progression-free survival (mPFS) in older patients was 8.5, 26.2 months, and not reached with letrozole + temsirolimus, palbociclib, and ribociclib, respectively, and in younger patients was 9.0, 18.8 months, and not reached, respectively. In the second-line setting, older patients had mPFS of 6.8 and 9.9 months with everolimus + exemestane and palbociclib + fulvestrant, respectively, and younger patients had mPFS of 8.1 and 9.5 months, respectively. Tolerability was worse for combination therapy versus monotherapy. No age-related differences in discontinuations were observed for CDK4/6 inhibitors, although a higher rate of treatment discontinuation was observed for patients ≥ 70 years receiving everolimus + exemestane. Adverse event rates were similar in age-stratified subsets.
ET + CDK4/6 or mTOR inhibitors are likely safe and effective in older patients with HR+, HER2− advanced breast cancer.
KeywordsElderly Breast cancer Geriatric CDK4/6 inhibitor Ribociclib Palbociclib
Editorial assistance was provided under the direction of the authors by Jonathan Morgan, Ph.D., and David Boffa, ELS, MedThink SciCom.
This study was funded by Novartis Pharmaceuticals Corporation. Rachel Freedman receives funding from Susan G. Komen and the American Cancer Society.
Compliance with ethical standards
Conflict of interest
Rachel Freedman receives research funding (institutional) from Eisai and Puma Biotechnology. Sara Tolaney receives research funding (institutional) from Novartis Pharmaceuticals Corporation, Eli Lilly and Co, Pfizer, Exelixis, Eisai, Merck, Genentech, AstraZeneca, Cyclacel, and Nektar Therapeutics, and she serves as a consultant to Eli Lilly and Co, Novartis Pharmaceuticals Corporation, Pfizer, Eisai, Sanofi, Merck, AstraZeneca, and Nektar Therapeutics. This study was supported by Novartis Pharmaceuticals Corporation.
Research involving human and animal rights
This article does not contain any studies with human participants or animals performed by any of the authors.
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