A Phase II Study of Pembrolizumab in Combination with Capecitabine and Oxaliplatin with Molecular Profiling in Patients with Advanced Biliary Tract Carcinoma. (19th February 2022)

• Record Type: Journal Article
• Authors: Monge, Cecilia; Pehrsson, Erica C; Xie, Changqing; Duffy, Austin G; Mabry, Donna; Wood, Bradford J; Kleiner, David E; Steinberg, Seth M; Figg, William D; Redd, Bernadette; Budhu, Anuradha; Wang, Sophie; Tandon, Mayank; Ma, Lichun; Wei Wang, Xin; Greten, Tim F
• Is Part Of: Oncologist. Volume 27:Number 3(2022)
• Page Start: e273
• Page End: e285
• Publication Date: 2022-02-19
• Subjects: biliary tract cancer -- cholangiocarcinoma -- capecitabine -- oxaliplatin -- pembrolizumab -- single-cell sequencing -- RNA-sequencing -- clonal evolution -- PD-L1; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1093/oncolo/oyab073
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract: Background: We conducted a phase II study of the combination of pembrolizumab with capecitabine and oxaliplatin (CAPOX) in patients with advanced biliary tract carcinoma (BTC) to assess response rate and clinical efficacy. Exploratory objectives included correlative studies of immune marker expression, tumor evolution, and immune infiltration in response to treatment. Patients and Methods: Adult patients with histologically confirmed BTC were enrolled and received oxaliplatin and pembrolizumab on day 1 of cycles 1-6. Capecitabine was administered orally twice daily as intermittent treatment, with the first dose on day 1 and the last dose on day 14 of cycles 1-6. Starting on cycle 7, pembrolizumab monotherapy was continued until disease progression. The primary endpoint was progression-free survival (PFS). Secondary endpoints were safety, tolerability, feasibility, and response rate. Immunohistochemistry (IHC) for PD-L1 and immune infiltrates was analyzed in paired tumor biopsies, as well as bulk transcriptome and exome profiling for five patients and single-cell RNA sequencing for one partial responder. Results: Eleven patients enrolled, three of whom had received no prior systemic therapy. Treatment was well tolerated, and the most common treatment-related grade 3 or 4 adverse events were lymphocytopenia, anemia, and decreased platelet count. Three patients (27.3%) achieved a partial response, and six (54%) had stable disease. The disease control rate was 81.8%. The median PFS was 4.1 months with a 6-month PFS rate of 45.5%. Molecular profiling suggests qualitative differences in immune infiltration and clonal evolution based on response. Conclusion: Capecitabine and oxaliplatin in combination with pembrolizumab is tolerable and a potentially effective treatment for refractory advanced BTC. This study highlights a design framework for the precise characterization of individual BTC tumors. Trial Registration: This study was registered in ClinicalTrials.gov (NCT03111732). Abstract : This article reports results of a phase II study of the combination of pembrolizumab with capecitabine and oxaliplatin in patients with advanced biliary tract carcinoma to assess response rate and clinical efficacy.