Phase II Clinical Trial of Pembrolizumab and Chemotherapy Reveals Distinct Transcriptomic Profiles by Radiologic Response in Metastatic Triple-Negative Breast Cancer

• Published in: Clinical cancer research Vol. 30; no. 1; pp. 82 - 93
• Main Authors: Wilkerson, Avia D, Parthasarathy, Prerana Bangalore, Stabellini, Nickolas, Mitchell, Carley, Pavicic, Jr, Paul G, Fu, Pingfu, Rupani, Amit, Husic, Hana, Rayman, Patricia A, Swaidani, Shadi, Abraham, Jame, Budd, G Thomas, Moore, Halle, Al-Hilli, Zahraa, Ko, Jennifer S, Baar, Joseph, Chan, Timothy A, Alban, Tyler, Diaz-Montero, C Marcela, Montero, Alberto J
• Format: Journal Article
• Language: English
• Published: United States 05.01.2024
• Subjects: Antibodies, Monoclonal, Humanized - pharmacology; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Gene Expression Profiling; Humans; Progression-Free Survival; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - pathology
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-23-1349

A single arm, phase II trial of carboplatin, nab-paclitaxel, and pembrolizumab (CNP) in metastatic triple-negative breast cancer (mTNBC) was designed to evaluate overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), safety/tolerability, overall survival (OS), and identify pathologic and transcriptomic correlates of response to therapy. Patients with ≤2 prior therapies for metastatic disease were treated with CNP regardless of tumor programmed cell death-ligand 1 status. Core tissue biopsies were obtained prior to treatment initiation. ORR was assessed using a binomial distribution. Survival was analyzed via the Kaplan-Meier method. Bulk RNA sequencing was employed for correlative studies. Thirty patients were enrolled. The ORR was 48.0%: 2 (7%) complete responses (CR), 11 (41%) partial responses (PR), and 8 (30%) stable disease (SD). The median DOR for patients with CR or PR was 6.4 months [95% confidence interval (CI), 4-8.5 months]. For patients with CR, DOR was >24 months. Overall median PFS and OS were 5.8 (95% CI, 4.7-8.5 months) and 13.4 months (8.9-17.3 months), respectively. We identified unique transcriptomic landscapes associated with each RECIST category of radiographic treatment response. In CR and durable PR, IGHG1 expression was enriched. IGHG1high tumors were associated with improved OS (P = 0.045) and were concurrently enriched with B cells and follicular helper T cells, indicating IGHG1 as a promising marker for lymphocytic infiltration and robust response to chemo-immunotherapy. Pretreatment tissue sampling in mTNBC treated with CNP reveals transcriptomic signatures that may predict radiographic responses to chemo-immunotherapy.