Molecular predictors of response to pembrolizumab in thymic carcinoma
Yongfeng He, Archana Ramesh, Yuriy Gusev, Krithika Bhuvaneshwar, Giuseppe Giaccone, Yongfeng He, Archana Ramesh, Yuriy Gusev, Krithika Bhuvaneshwar, Giuseppe Giaccone
Abstract
Thymic carcinoma is rare and has a poorer prognosis than thymomas. The treatment options are limited after failure of platinum-based chemotherapy. We previously performed a single-center phase II study of pembrolizumab in patients with advanced thymic carcinoma, showing a 22.5% response rate. Here, we characterize the genomic and transcriptomic profile of thymic carcinoma samples from 10 patients (5 non-responders versus 5 responders) in this cohort, with the main aim of identifying potential predictors of response to immunotherapy. We find that expression of PDL1 and alterations in genes or pathways that correlated with PD-L1 expression (CYLD and BAP1) could be potential predictors for response or resistance to immunotherapy in patients with advanced thymic carcinoma. Our study provides insights into potential predictive markers/pathways to select patients with thymic carcinoma for anti-PD-1 immunotherapy.
Trial registration: ClinicalTrials.gov NCT02364076.
Keywords: immune checkpoint inhibitors; predictors of response; thymic carcinoma; whole exome sequencing; whole-transcriptome sequencing.
Conflict of interest statement
The authors have declared that no competing interests exist.
© 2021 The Author(s).
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