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Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer |
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| Authors: | Takayuki Yoshino Thierry Andre Tae Won Kim Wei Peng Yong Kai-Keen Shiu Benny Vittrup Jensen Lars Henrik Jensen Cornelis J A Punt Denis Smith Rocio Garcia-Carbonero Julia Alcaide-Garcia Peter Gibbs Christelle de la Fouchardiere Fernando Rivera Elena Elez Dung T Le Noriaki Adachi David Fogelman Patricia Marinello Luis A Diaz Jr |
| Institution: | 1. National Cancer Center Hospital East, Kashiwa, Chiba, Japan;2. Department of Medical Oncology, Sorbonne University, Saint-Antoine Hospital, AP-HP, INSERM 938, SIRIC CURAMUS, Paris, France;3. Asan Medical Center, University of Ulsan, Seoul, South Korea;4. National University Hospital, National University Cancer Institute, Singapore, Singapore;5. University College Hospital, NHS Foundation Trust, London, UK;6. Herlev and Gentofte Hospital, Herlev, Denmark;7. University Hospital of Southern Denmark, Vejle, Denmark;8. Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands;9. Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France;10. Hospital Universitario 12 de Octubre, Imas12, Universidad Complutense de Madrid (UCM), Madrid, Spain;11. Unidad de Gestión Clínica Intercentros de Oncología Médica, Hospitales Universitarios Regional y Virgen de la Victoria, IBIMA, Malaga, Spain;12. Western Hospital, Footscray, Victoria, Australia;13. Centre Léon Bérard, Lyon, France;14. Fernando Rivera, University Hospital Marqués de Valdecilla, IDIVAL, Santander, Spain;15. Vall d'Hebron Barcelona Hospital Campus, Vall D'Hebron Institute of Oncology, Universitat Autònoma de Barcelona, Barcelona, Spain;16. The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, Maryland, USA;17. Merck & Co., Inc., Rahway, New Jersey, USA;18. Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA |
| Abstract: | The phase 3 KEYNOTE-177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite-instability-high (MSI-H)/mismatch-repair-deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression-free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE-177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval CI] 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio HR] 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment-related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune-mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first-line pembrolizumab as a standard of care for patients from Asia with MSI-H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002. |
| Keywords: | Asia colorectal cancer microsatellite instability mismatch-repair deficiency pembrolizumab |