Invited discussant of the KEYNOTE-355 trial, Hope S. Rugo, MD, FASCO, one of the coauthors of the study, had presented the survival data at the 2021 European Society of Medical Oncology (ESMO) Annual Congress.1 The San Antonio presentation was a more in-depth evaluation of survival by different PD-L1 cutoffs, as measured by combined positive score (CPS).
“The KEYNOTE-355 trial included pembrolizumab plus background chemotherapy and demonstrated improved overall survival and progression-free survival in patients with a CPS ≥ 10. Results demonstrated a CPS of 10 as the optimal cutoff, confirming pembrolizumab and chemotherapy as standard of care in this population,” Dr. Rugo stated.
Several questions remain, however, Dr. Rugo said. In metastatic triple-negative breast cancer, “PD-L1 is an imperfect marker but the best one we have at present. Why is a PD-L1 CPS score important for metastatic disease alone? More data are needed to match antibody tests to specific CPS scores. Is there a best chemotherapy partner? Why was IMpassion131 a negative trial? Was it because of triple-negative breast cancer heterogeneity? How long should a checkpoint inhibitor be continued in excellent responders? At some point, we need to stop therapy,” she commented.
Hope S. Rugo, MD, FASCO
Roadmap for Treatment
Approximately 38% of patients with triple-negative breast cancer benefit from pembrolizumab, and Dr. Rugo said that ongoing studies are addressing how to amplify the immune response in patients who don’t have a good response. Strategies under study to boost the immune response include induction with chemotherapy and combinations of checkpoint inhibitors with other treatments, such as antibody-drug conjugates, PARP inhibitors, and radiotherapy.
“The roadmap for treatment should be based on PD-L1 testing and germline status. Always consider clinical trials at each time point,” Dr. Rugo stated.
DISCLOSURE: Dr. Rugo has served as a consultant or advisor to Puma Biotechnology, Napo, and Samsung; has received institutional research funding from AstraZeneca, Ayala, Boehringer Ingelheim, Daiichi Sankyo, Genentech, Gilead, Lilly, Merck, Novartis, OBI Pharma, Pfizer, Polyphor, Sermonix, and Seattle Genetics.
1. Rugo HS, Cortes J, Cescon DW, et al: KEYNOTE-355: Final results from a randomized, double-blind phase III study of first-line pembrolizumab + chemotherapy vs placebo + chemotherapy for metastatic TNBC. 2021 ESMO Annual Congress. Abstract LBA16. Presented September 19, 2021.
Results of the phase III randomized KEYNOTE-355 trial showed that the addition of the PD-1 inhibitor pembrolizumab to investigator’s choice of first-line chemotherapy improved progression-free and overall survival in women with metastatic triple-negative breast cancer compared with placebo and...