Key Questions for Improving Outcomes With Pembrolizumab in PD-L1+ TNBC

Lee Schwartzberg, MD, chief medical director of West Cancer Center and chief of the division of hematology/oncology at the University of Tennessee Health Science Center, discusses important questions that have been raised due to the positive results of pembrolizumab (Keytruda) immunotherapy for patients with triple-negative breast cancer (TNBC).

The phase 3 KEYNOTE-355 trial (NCT02819518) demonstrated the efficacy of pembrolizumab plus chemotherapy in metastatic PD-L1–positive TNBC, while the KEYNOTE-522 trial (NCT03036488) showed efficacy of pembrolizumab and chemotherapy in the adjuvant and neoadjuvant setting. These studies made pembrolizumab a standard-of-care for PD-L1–positive patients.

Some questions that are unanswered by these studies include the significance of chemotherapy. Schwartzberg suggests investigating whether aggressive chemotherapy is required, and which components of the regimen are most effective, such as anthracyclines or platinum-based agents.

Another question is whether pembrolizumab should be continued in the adjuvant and neoadjuvant setting even after a pathologic complete response (pCR) has been achieved. Schwartzberg says that the KEYNOTE-522 study found a 2% difference in survival outcomes in favor of continuing receiving pembrolizumab, but the study was not designed to compare its contribution in the adjuvant versus neoadjuvant phase.

TRANSCRIPTION:

0:08 | There's lots of questions that are still left after these studies, we have a new standard of care for stage II and III triple-negative breast cancer in the early setting. And we have a new standard-of-care for the 40% of patients in a PD-L1–positive metastatic setting, but it leaves many questions. And some of those questions are: do we need that aggressive chemotherapy with pembrolizumab? What's the most important component of that chemotherapy? What of those agents synergize with the pembrolizumab? There was some evidence in anthracyclines might... there's some evidence that that platinum might. Do we need to continue pembrolizumab after achieving a pCR? There was a 2% difference in outcome favoring continuing it, but we don't really know what that really means.