Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer Journal Article
| Authors: | Yoshino, T.; Andre, T.; Kim, T. W.; Yong, W. P.; Shiu, K. K.; Jensen, B. V.; Jensen, L. H.; Punt, C. J. A.; Smith, D.; Garcia-Carbonero, R.; Alcaide-Garcia, J.; Gibbs, P.; de la Fouchardiere, C.; Rivera, F.; Elez, E.; Le, D. T.; Adachi, N.; Fogelman, D.; Marinello, P.; Diaz, L. A. Jr |
| Article Title: | Pembrolizumab in Asian patients with microsatellite-instability-high/mismatch-repair-deficient colorectal cancer |
| 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. © 2022 Merck Sharp & Dohme LLC and The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. |
| Keywords: | adult; clinical article; controlled study; aged; overall survival; fatigue; neutropenia; bevacizumab; cancer combination chemotherapy; diarrhea; drug safety; drug withdrawal; hypertension; side effect; cancer patient; antineoplastic agent; colorectal cancer; progression free survival; multiple cycle treatment; neutrophil count; sensory neuropathy; anemia; nausea; randomized controlled trial; stomatitis; vomiting; antineoplastic combined chemotherapy protocols; peripheral neuropathy; colonic neoplasms; continuous infusion; pathology; cetuximab; microsatellite dna; irinotecan; monoclonal antibody; alanine aminotransferase blood level; aspartate aminotransferase blood level; fever; gamma glutamyl transferase blood level; pneumonia; rash; colorectal neoplasms; alanine aminotransferase; aspartate aminotransferase; malaise; adverse outcome; multicenter study; colorectal tumor; folinic acid; mismatch repair; colon tumor; microsatellite instability; dna mismatch repair; hyperpigmentation; colitis; open study; asia; dermatitis; phase 3 clinical trial; leukocyte count; hyperthyroidism; hypothyroidism; oxaliplatin; gamma glutamyltransferase; hand foot syndrome; alopecia; epistaxis; japan; fluoropyrimidine; proteinuria; taiwan; urticaria; platelet count; paronychia; hypesthesia; microsatellite repeats; adrenal insufficiency; post hoc analysis; asian; decreased appetite; hypersensitivity; korea; overall response rate; singapore; response evaluation criteria in solid tumors; antibodies, monoclonal, humanized; humans; human; male; female; article; pembrolizumab; mismatch-repair deficiency |
| Journal Title: | Cancer Science |
| Volume: | 114 |
| Issue: | 3 |
| ISSN: | 1347-9032 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2023-03-01 |
| Start Page: | 1026 |
| End Page: | 1036 |
| Language: | English |
| DOI: | 10.1111/cas.15650 |
| PUBMED: | 36369901 |
| PROVIDER: | scopus |
| PMCID: | PMC9986093 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
