Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer
Yoshino, Takayuki (National Cancer Center Hospital East)
André, Thierry (Sorbonne University)
Kim, Tae Won (University of Ulsan)
Yong, Wei Peng (National University Cancer Institute)
Shiu, Kai-Keen (University College Hospital)
Jensen, Benny Vittrup (Herlev and Gentofte Hospital)
Jensen, Lars Henrik (University Hospital of Southern Denmark)
Punt, Cornelis J. A. (University Medical Center Utrecht)
Smith, Denis (Hôpital Haut-Lévêque)
García-Carbonero, Rocío (Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12))
Alcaide-Garcia, Julia (Hospital Universitario Virgen de la Victoria (Màlaga, Andalusia))
Gibbs, Peter (Western Hospital)
de la Fouchardiere, Christelle (Centre Léon Bérard)
Rivera, Fernando (Hospital Universitario Marqués de Valdecilla (Santander, Cantabria))
Elez, Elena (Vall d'Hebron Institut d'Oncologia)
Le, Dung T. (Johns Hopkins Medicine)
Adachi, Noriaki (Merck (Estats Units d'Amèrica))
Fogelman, David (Merck(Estats Units d'Amèrica))
Marinello, Patricia (Merck (Estats Units d'Amèrica))
Diaz, Luis A. (Memorial Sloan Kettering Cancer Center)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	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. identifier: NCT02563002. We report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis of the phase 3 KEYNOTE-177 study which 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). Median PFS was not reached (NR) with pembrolizumab versus 10. 4 months with chemotherapy (hazard ratio [HR] 0. 56, 95% confidence interval [CI] 0. 26-1. 20]), median OS was NR versus 30. 0 months (HR 0. 65, 95% CI 0. 27-1. 55), ORR was 50% versus 46%, and grade 3/4 treatment-related adverse events were reported by two patients (9%) versus 20 (80%). These data support first-line pembrolizumab as a standard of care for patients from Asia with MSI-H/dMMR mCRC.
Nota:	Altres ajuts: Merck Sharp and Dohme
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, i la comunicació pública de l'obra, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original. No es permet la creació d'obres derivades.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Asia ; Colorectal cancer ; Microsatellite instability ; Mismatch-repair deficiency ; Pembrolizumab
Publicat a:	Cancer Science, Vol. 114 (december 2022) , p. 1026-1036, ISSN 1349-7006

DOI: 10.1111/cas.15650
PMID: 36369901

11 p, 458.4 KB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats