Journal
CLINICAL CANCER RESEARCH
Volume 27, Issue 19, Pages 5299-5306Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-21-0607
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Funding
- Susan G. Komen Career Catalyst Grant [CCRCR18552647]
- NIH/NCI SPORE [2P50CA098131-17]
- Department of Defense Era of Hope [BC170037]
- Vanderbilt-Ingram Cancer Center Support Grant [P30 CA68485]
- NIH [T32GM007347, F30CA236157]
- Gateway for Cancer Research [G-16-900]
- QuantumLeap Healthcare Collaborative
- Foundation for the NIH
- NCI Center for Biomedical Informatics and Information Technology [28XS197]
- Sta Op Tegen Kanker International Translational Cancer Research Grant
- Safeway Foundation
- Bill Bowes Foundation
- Quintiles Transnational
- Johnson Johnson
- Genentech
- Amgen
- San Francisco Foundation
- Give Breast Cancer the Boot
- Eli Lilly
- Pfizer
- Eisai
- Harlan family
- Avon Foundation for Women
- Alexandria Real Estate Equities
- AstraZeneca
- NCI [R01CA219647]
- Breast Cancer Research Foundation
- Susan Komen Foundation Leadership Grant [SAC 160076]
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The study investigated the predictive value of MHC-II expression on tumor cells for the benefit of adding immunotherapy to standard neoadjuvant chemotherapy in HER2-negative breast cancer. The findings suggest that quantitative assessment of MHC-II expression can predict the effectiveness of immunotherapy when combined with standard NAC, but not when used alone. Validation in future clinical trials is recommended.
Purpose: Immunotherapies targeting PD-1/L1 enhance pathologic complete response (pCR) rates when added to standard neoadjuvant chemotherapy (NAC) regimens in early-stage triple-negative, and possibly high-risk estrogen receptor-positive breast cancer. However, immunotherapy has been associated with significant toxicity, and most patients treated with NAC do not require immunotherapy to achieve pCR. Biomarkers discerning patients benefitting from the addition of immunotherapy from those who would achieve pCR to NAC alone are clearly needed. In this study, we tested the ability of MHC-II expression on tumor cells, to predict immunotherapy-specific benefit in the neoadjuvant breast cancer setting. Patients and Methods: This was a retrospective tissue-based analysis of 3 cohorts of patients with breast cancer: (i) primary nonimmunotherapy-treated breast cancers (n = 381), (ii) triple-negative breast cancers (TNBC) treated with durvalumab and standard NAC (n = 48), and (iii) HER2-negative patients treated with standard NAC (n = 87) or NAC and pembrolizumab (n = 66). Results: HLA-DR positivity on >= 5% of tumor cells, defined a priori, was observed in 10% and 15% of primary non-immunotherapy-treated hormone receptor-positive and triple-negative breast cancers, respectively. Quantitative assessment of MHC-II on tumor cells was predictive of durvalumab + NAC and pembrolizumab + NAC (ROC AUC, 0.71; P = 0.01 and AUC, 0.73; P = 0.001, respectively), but not NAC alone (AUC, 0.5; P = 0.99). Conclusions: Tumor-specific MHC-II has a strong candidacy as a specific biomarker of anti-PD-1/L1 immunotherapy benefit when added to standard NAC in HER2-negative breast cancer. Combined with previous studies in melanoma, MHC-II has the potential to be a pan-cancer biomarker. Validation is warranted in existing and future phase II/III clinical trials in this setting.
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