Efficacy of Pembrolizumab in Patients With Noncolorectal High Microsatellite Instability/Mismatch Repair-Deficient Cancer: Results From the Phase II KEYNOTE-158 Study.
By A. Marabelle, D. Le, P. Ascierto, A. D. Di Giacomo, A. De Jesus-Acosta, J. Delord, R. Geva, M. Gottfried, N. Penel, A. Hansen and 12 more. Journal of Clinical Oncology, 2020
2,394 citations recorded by the source corpus.
PURPOSE Genomes of tumors that are deficient in DNA mismatch repair (dMMR) have high microsatellite instability (MSI-H) and harbor hundreds to thousands of somatic mutations that encode potential neoantigens. Such tumors are therefore likely to be immunogenic, triggering upregulation of immune checkpoint proteins. Pembrolizumab, an anti‒programmed death-1 monoclonal antibody, has antitumor activity against MSI-H/dMMR cancer. We report data from the phase II KEYNOTE-158 study of pembrolizumab in patients with previously treated, advanced noncolorectal MSI-H/dMMR cancer. PATIENTS AND METHODS Eligible patients with histologically/cytologically confirmed MSI-H/dMMR advanced noncolorectal cancer who experienced failure with prior therapy received pembrolizumab 200 mg once every 3 weeks for 2 years or until disease progression, unacceptable toxicity, or patient withdrawal. Radiologic imaging was performed every 9 weeks for the first year of therapy and every 12 weeks thereafter. The primary end point was objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as assessed by independent central radiologic review. RESULTS Among 233 enrolled patients, 27 tumor types were represented, with endometrial, gastric, cholangiocarcinoma, and pancreatic cancers being the most common. Median follow up was 13.4 months. Objective response rate was 34.3% (95% CI, 28.3% to 40.8%). Median progression-free survival was 4.1 months (95% CI, 2.4 to 4.9 months) and median overall survival was 23.5 months (95% CI, 13.5 months to not reached). Treatment-related adverse events occurred in 151 patients (64.8%). Thirty-four patients (14.6%) had grade 3 to 5 treatment-related adverse events. Grade 5 pneumonia occurred in one patient; there were no other treatment-related fatal adverse events. CONCLUSION Our study demonstrates the clinical benefit of anti-programmed death-1 therapy with pembrolizumab among patients with previously treated unresectable or metastatic MSI-H/dMMR noncolorectal cancer. Toxicity was consistent with previous experience of pembrolizumab monotherapy.
Subfields: Epidemiology, Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/dcc30a76604d64b48ca67e47edd2aae57142061b
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Citations in the corpus
- Phase II Open-Label Study of Pembrolizumab in Treatment-Refractory, Microsatellite Instability–High/Mismatch Repair–Deficient Metastatic Colorectal Cancer: KEYNOTE-164 (2019, neutral): “Median tumor size, mm (range) 99 (11-408) 60 (10-307)”
- Acquired Resistance to Immune Checkpoint Inhibitors (2020, background): “We have attempted to infer the rates of acquired resistance based upon available duration of response data among different tumor types (Antonia et al., 2019; Armand et al., 2018; Balar et al., 2018; Burtness et al., 2019; Chen et al., 2019a; Cohen et al., 2019; Fehrenbacher et al., 2018; Fradet et a”
- Pancreatic Adenocarcinoma, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. (2021, background): “5 months.(214) Pembrolizumab is recommended by the NCCN Panel for the advanced disease setting for first-line and subsequent treatment as appropriate.”
- Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer. (2020, neutral): “Peripheral neuropathy 1 (1) 0 27 (19) 1 (1)”