Phase I/II trial of palbociclib, pembrolizumab and letrozole in patients with hormone receptor-positive metastatic breast cancer

• Published in: European journal of cancer (1990) Vol. 154; pp. 11 - 20
• Main Authors: Yuan, Yuan, Lee, Jin Sun, Yost, Susan E., Frankel, Paul H., Ruel, Christopher, Egelston, Colt A., Guo, Weihua, Padam, Simran, Tang, Aileen, Martinez, Norma, Schmolze, Daniel, Presant, Cary, Ebrahimi, Behnam, Yeon, Christina, Sedrak, Mina, Patel, Niki, Portnow, Jana, Lee, Peter, Mortimer, Joanne
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2021; Elsevier Science Ltd
• Subjects: Adult; Adverse events; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers; Biomarkers, Tumor; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - mortality; CDK 4/6 inhibitor; Clinical trials; Confidence intervals; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - antagonists & inhibitors; Cyclin-Dependent Kinase 6 - antagonists & inhibitors; Epidermal growth factor; ErbB-2 protein; Female; Growth factors; Hormone receptor positive; Humans; Immune checkpoint inhibitor; Immune Checkpoint Inhibitors - administration & dosage; Immune response; Immune system; Immunotherapy; Inhibitors; Letrozole - administration & dosage; Metastases; Metastasis; Metastatic breast cancer; Middle Aged; Neutropenia; Pembrolizumab; Piperazines - administration & dosage; Priming; Pyridines - administration & dosage; Receptors; Receptors, Estrogen - analysis; Safety; Solid tumors; Survival; Thrombocytopenia; Tumors; Metastatic breast cancer; Immune checkpoint inhibitor; CDK 4/6 inhibitor; Hormone receptor positive
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2021.05.035

CDK4/6 inhibitors modulate immune response in breast cancer. This phase I/II trial was designed to test the safety and efficacy of palbociclib, pembrolizumab and letrozole in women with hormone receptor positive (HR+) human epidermal growth factor receptor 2 negative (HER2−) metastatic breast cancer (MBC). Women with stage IV HR+ HER2− MBC were enrolled and treated with palbociclib, pembrolizumab and letrozole. Primary end-points were safety, tolerability and efficacy. Between November 2016 and July 2020, 23 patients were enrolled with 20 evaluable for response, including 4 patients in cohort 1 and 16 patients in cohort 2. Cohort 1 median age was 48 years (33–70) and cohort 2 median age was 55 (37–75). Cohort 1 closed early due to limited accrual. Grade III–IV adverse events were neutropenia (83%), leucopaenia (65%), thrombocytopenia (17%) and elevated liver enzymes (17%). In cohort 1, 50% achieved a partial response (PR) and 50% had stable disease (SD). In cohort 2, 31% achieved complete response (CR), 25% had PR and 31% had SD by Response Evaluation Criteria in Solid Tumours version 1.1. Median progression-free survival was 25.2 months (95% confidence interval [CI] 5.3, not reached) and median overall survival was 36.9 months (95% CI 36.9, not reached) in cohort 2 with a median follow-up of 24.8 months (95% CI 17.1, not reached). A correlative immune biomarker analysis was published separately. The combination of palbociclib, pembrolizumab and letrozole is well tolerated, and a complete response rate of 31% was identified in HR+ MBC patients who received this combination as front-line therapy. Confirmatory trials are required to better understand the immune-priming effects of CDK4/6 inhibitors. •Palbociclib, pembrolizumab and AI are safe in HR+ metastatic BC patients.•Median PFS is 25.2 months.•Combination has a CR rate of 31% in HR+ metastatic BC patients.