Invited discussant Laura Huppert, MD, of the University of California, San Francisco, Comprehensive Cancer Center, focused her remarks on the need for biomarkers for selection of immunotherapy as part of neoadjuvant chemotherapy for hormone receptor–positive, HER2-negative breast cancer.

“Hormone receptor–positive, HER2-negative breast cancer is heterogeneous, and pathologic complete response varies by subtypes. In general, the pathologic complete response rates to neoadjuvant chemotherapy are low,” she told listeners.

Studies have shown that the addition of immunotherapy to neoadjuvant chemotherapy improves pathologic complete response rate and event-free survival in triple-negative breast cancer. “Thus far, the KEYNOTE-756 and CheckMate 7FL studies both showed that immunotherapy added to neoadjuvant chemotherapy improves pathologic complete response rates in patients with hormone receptor–positive, HER2-negative early-stage breast cancer, but the effect on event-free survival is immature,” she said.

Laura Huppert, MD

With the caveat that cross-trial comparisons have limitations, Dr. Huppert looked at biomarker data from two recent studies of immunotherapy added to neoadjuvant chemotherapy in hormone receptor–positive/HER2-negative breast cancer: KEYNOTE-756 (pembrolizumab) and CheckMate 7FL (nivolumab).¹ In KEYNOTE-756, there was benefit of adding pembrolizumab in patients with early-stage hormone receptor–positive/HER2-negative breast cancer particularly if patients were PD-L1–positive (with increasing benefit with higher 22C3 combined positive scores [CPS]) and in patients with low estrogen receptor (ER) positivity (ER expression < 10%). The benefit of pembrolizumab was less clear in patients with a 22C3 CPS < 1 and those with ER expression > 10%. Similarly, in CheckMate 7FL, patients with early-stage hormone receptor–positive/HER2-negative breast cancer who were PD-L1–positive and had low ER percent positivity (< 50%) derived the most benefit from the addition of nivolumab, whereas benefit was less clear in breast cancers that were PD-L1–negative and had a high ER status (> 50%). They also demonstrated that patients who had a stromal tumor infiltrating lymphocytes > 1% derived more benefit with the addition of nivolumab. There was no association between Ki67 status and the benefit of nivolumab.

These observations are preliminary, and event-free survival data are awaited, Dr. Huppert said.

DISCLOSURE: Dr. Huppert has served as a consultant to AstraZeneca and Pfizer.

REFERENCE

1. Loi S, Curigliano G, Salgado RF, et al: A randomized, double-blind trial of nivolumab vs placebo with neoadjuvant chemotherapy followed by adjuvant endocrine therapy ± nivolumab in patients with high-risk, ER+ HER2– primary breast cancer. ESMO Congress 2023. Abstract LBA20. Presented October 20, 2023.