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

Autor:	Wilkerson AD; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio.; Cleveland Clinic Digestive Disease & Surgery Institute, Department of General Surgery, Cleveland, Ohio., Parthasarathy PB; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio., Stabellini N; Graduate Education Office, Case Western Reserve University School of Medicine, Cleveland, Ohio., Mitchell C; University Hospitals Cleveland Medical Center, Department of Internal Medicine, Cleveland, Ohio., Pavicic PG Jr; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio., Fu P; Case Western Reserve University, Department of Population and Quantitative Health Sciences, Cleveland, Ohio., Rupani A; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio., Husic H; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio., Rayman PA; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio., Swaidani S; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio., Abraham J; Cleveland Clinic Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland, Ohio., Budd GT; Cleveland Clinic Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland, Ohio., Moore H; Cleveland Clinic Department of Hematology and Medical Oncology, Taussig Cancer Center, Cleveland, Ohio., Al-Hilli Z; Cleveland Clinic Digestive Disease & Surgery Institute, Department of General Surgery, Cleveland, Ohio., Ko JS; Cleveland Clinic Pathology & Laboratory Medicine, Department of Anatomic Pathology, Cleveland, Ohio., Baar J; University Hospitals/Seidman Cancer Center Case Western Reserve University, Cleveland, Ohio., Chan TA; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio., Alban T; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio., Diaz-Montero CM; Cleveland Clinic Lerner Research Institute, Center for Immunotherapy & Precision Immuno-Oncology, Cleveland, Ohio., Montero AJ; University Hospitals/Seidman Cancer Center Case Western Reserve University, Cleveland, Ohio.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2024 Jan 05; Vol. 30 (1), pp. 82-93.
DOI:	10.1158/1078-0432.CCR-23-1349
Abstrakt:	Purpose: 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 and Methods: 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. Results: 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. Conclusions: Pretreatment tissue sampling in mTNBC treated with CNP reveals transcriptomic signatures that may predict radiographic responses to chemo-immunotherapy. (©2023 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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