Justin Balko, PharmD, Ph.D. from Vanderbilt University Medical Center speaks about Tumor-specific major histocompatibility-II expression predicts benefit to anti-PD-1/L1 therapy in patients with HER2-negative primary breast cancer.
Link to Article:
https://clincancerres.aacrjournals.org/content/early/2021/07/22/1078-0432.CCR-21-0607
Abstract:
Intention:
When combined with conventional neoadjuvant chemotherapy (NAC), immunotherapies targeting PD-1/L1 improve pathologic complete response (pCR) rates in early-stage triple-negative and perhaps high-risk estrogen receptor-positive breast cancer. Immunotherapy, on the other hand, has been linked to substantial toxicity, and most patients treated with NAC do not require it to reach pCR. Biomarkers that can distinguish individuals who will benefit from immunotherapy from those who will achieve pCR with NAC alone are obviously needed. The capacity of MHC-II expression on tumor cells to predict immunotherapy-specific effectiveness in the neoadjuvant breast cancer scenario was investigated in this study. Patients and Procedures: This study looked at three groups of breast cancer patients: 1) initial non-immunotherapy-treated breast cancers (n=381), 2) TNBCs treated with durvalumab and standard NAC (n=48), and 3) HER2-negative patients treated with normal NAC (n=87) or NAC plus pembrolizumab (n=66). Results: HLA-DR positivity on greater than or equal to 5% of tumor cells, as defined a priori, was found in 10% and 15% of HR+ and triple-negative breast cancers, respectively, in primary non-immunotherapy-treated HR+ and triple-negative breast cancers. Durvalumab + NAC and pembrolizumab + NAC (receiver-operator characteristic [ROC] AUC 0.71; p=0.01 and AUC 0.73; p=0.001, respectively) were predicted by quantitative evaluation of MHC-II on tumor cells, but not NAC alone (AUC 0.5; p=0.99). Conclusions: When combined with conventional NAC, tumor-specific MHC-II has a good case for being a particular biomarker of anti-PD-1/L1 immunotherapy benefit in HER2-negative breast cancer. MHCII has the potential to be a pan-cancer biomarker when combined with prior findings in melanoma. Existing and prospective Phase II/III clinical studies in this context should be validated.