Yuan Yuan, MD, PhD
Yuan Yuan, MD, PhD, a medical oncologist at City of Hope, Duarte, California, weighed in on the KEYNOTE-355 findings.
“The study presented by Dr. Rugo on KEYNOTE-355 reconfirms the utility of adding immune checkpoint inhibitors to chemotherapy as front-line treatment for metastatic triple-negative breast cancer. The recent data discussed at the 2020 San Antonio Breast Cancer Symposium provided more granular information on the chemotherapy backbones. Although the study is not preplanned or powered for comparison among the chemotherapy backbones, all three pembrolizumab combination arms—including paclitaxel, nab-paclitaxel, and gemcitabine/carboplatin—showed statistically significant and clinically meaningful improvement in progression-free survival when compared with chemotherapy alone. The benefit across different chemotherapy regimens was consistently seen in patients with a CPS ≥ 1, and the impact is more pronounced in the CPS ≥ 10 group,” Dr. Yuan observed.
“The study is practice-changing with the recent approval by the U.S. Food and Drug Administration (FDA) based on results of this trial, although the current FDA approval is limited to tumors with a CPS of 10 or above. The study provides reassuring findings, supporting immune checkpoint inhibitor use with a chemotherapy regimen beyond nab-paclitaxel [as shown in IMpassion130]. More importantly, those patients who are ineligible for the taxane plus immune checkpoint inhibitor combination [especially those ‘fast progressors’ within 12 months of adjuvant or neoadjuvant taxane] would be able to benefit from the gemcitabine/carboplatin plus pembrolizumab combination,” Dr. Yuan explained.
Another Perspective
“KEYNOTE-355 confirmed and justified the enthusiasm that the breast cancer field has for adding immunotherapy to chemotherapy for patients with metastatic triple-negative breast cancer. Pembrolizumab was approved by the FDA for this indication in November 2020 based on the first report from KEYNOTE-355 showing improved progression-free survival. This update confirmed the progression-free survival benefit,” said Elizabeth Mittendorf, MD, PhD, of Brigham and Women’s Hospital; Co-Leader, Breast Program, Dana-Farber/Harvard Cancer Center; and Professor of Surgery, Harvard Medical School.
Elizabeth Mittendorf, MD, PhD
Dr. Mittendorf emphasized that, because pembrolizumab was of benefit regardless of the chemotherapy partner, clinicians now have good options for combination therapy.
“We still don’t know the overall survival data from KEYNOTE-355, but we do know from the IMpassion131 trial that studied atezolizumab in the same clinical setting that the addition of immunotherapy improved progression-free survival and overall survival. So, we are optimistic that this class of drugs will in fact improve overall survival,” Dr. Mittendorf noted.
She pointed out that patients have to be PD-L1–positive to receive pembrolizumab or atezolizumab. “The way PD-L1 positivity is assessed and defined varies with the different drugs. This means that oncologists are having ongoing discussions regarding the best way to assess PD-L1 status,” she added.
DISCLOSURE: Funding for the KEYNOTE-355 study was provided by Merck Sharp & Dohme Corp. Dr. Yuan has served as a consultant or advisor to Eisai, Genentech, Immunomedics, Novartis, and Pfizer; has participated in a speakers bureau for Eisai and Genentech; has received research funding from Eisai, Genentech, Merck, Novartis, Pfizer, and Puma Biotechnology; and has provided expert testimony on behalf of Novartis. Dr. Mittendorf has received honoraria from Physician Education Resource; has served as a consultant or advisor to Genomic Health, Merck, Peregrine Pharmaceuticals, Sellas Life Sciences, and TapImmune Inc; and has received institutional research funding from AstraZeneca, EMD Serono, Galena Biopharma, Genentech/Roche, and GlaxoSmithKline.
