Dr Niravath on Durvalumab, Trastuzumab, and Pertuzumab in HER2-Enriched Breast Cancer

“Patients with higher tumor-infiltrating lymphocytes [TILs], elevated PD-L1 combined positive scores [CPS], and lower cancer stages were more likely to achieve a pathologic complete response.”

Polly Niravath, MD, Lois E. and Carl A. Davis Centennial Chair in Cancer Research, Dr. Mary and Ron Neal Cancer Center, associate professor of clinical medicine, Academic Institute, Department of Medicine, Houston Methodist Hospital, discusses findings from a single-arm phase 2 study (NCT03820141) evaluating a chemotherapy-free regimen of trastuzumab (Herceptin) plus pertuzumab (Perjeta) and durvalumab (Imfinzi) in patients with HER2-enriched early breast cancer from the 2024 San Antonio Breast Cancer Symposium (SABCS).

The trial included 39 patients with HER2-enriched, estrogen receptor (ER)–negative/progesterone receptor (PR)–negative early-stage breast cancer. Patients received 6 cycles of durvalumab, trastuzumab, and pertuzumab as neoadjuvant therapy. The primary end point was the pathologic response (pRR) rate. Secondary analyses examined predictors of response, including clinical, pathologic, and genomic markers.

The study demonstrated a pRR rate of 67.6% and a pathologic complete response (pCR) rate of 48.6%. Patients with smaller tumors, earlier cancer stages, higher tumor-infiltrating lymphocyte (TIL) percentages, and elevated PD-L1 CPS were significantly more likely to achieve pCR. Additional analyses identified increased plasma and B-cell activity in the tumor microenvironment as a predictor of enhanced response, suggesting that immune activation plays a critical role in treatment efficacy.

The HER2DX genomic assay also emerged as a biomarker, with higher scores correlating with greater likelihood of achieving pCR, highlighting the importance of integrating immune and genomic profiling into treatment selection for patients with HER2-enriched breast cancer.

The regimen was well-tolerated, with no new safety signals observed. Niravath notes that the favorable safety and efficacy profile of the chemotherapy-free approach supports its potential as a viable option for select patients with HER2-enriched disease. Niravath concludes that these findings underscore the need for further research to validate predictive biomarkers and explore the application of this regimen, both in this patient population and beyond.