KEYNOTE-164 (NCT02460198) evaluated the antitumor activity of pembrolizumab in previously treated, metastatic, microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer ...(CRC).
This phase II open-label study involved 128 centers worldwide. Eligible patients were age ≥ 18 years and had metastatic MSI-H/dMMR CRC treated with ≥ 2 prior lines of standard therapy, including fluoropyrimidine, oxaliplatin, and irinotecan with or without anti-vascular endothelial growth factor/epidermal growth factor receptor monoclonal antibody (cohort A) or ≥ 1 prior line of therapy (cohort B). MSI-H/dMMR status was assessed locally. Patients received pembrolizumab 200 mg every 3 weeks for up to 2 years until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate by RECIST version 1.1 by independent central review. Secondary end points were duration of response, progression-free survival (PFS), overall survival, safety, and tolerability.
A total of 124 patients with MSI-H/dMMR CRC (61 in cohort A, 63 in cohort B) enrolled. At data cutoff, median follow-up was 31.3 months (range, 0.2-35.6 months) for cohort A and 24.2 months (range, 0.1-27.1 months) for cohort B. Objective response rate was 33% (95% CI, 21% to 46%) and 33% (95% CI, 22% to 46%), respectively, with median duration of response not reached in either cohort. Median PFS was 2.3 months (95% CI, 2.1 to 8.1 months) and 4.1 months (95% CI, 2.1 to 18.9 months). Median overall survival was 31.4 months (95% CI, 21.4 months to not reached) and not reached (95% CI, 19.2 months to not reached). Treatment-related grade 3-4 adverse events occurred in 10 patients (16%) in cohort A and 8 (13%) in cohort B, with the most common occurring in ≥ 2 patients being pancreatitis, fatigue, increased alanine aminotransferase, and increased lipase (2 patients each; 3%) in cohort A.
Pembrolizumab is effective with a manageable safety profile in patients with MSI-H/dMMR CRC.
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.
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.
The global, randomized, open-label KEYNOTE-183 phase 3 study was closed early after an interim analysis showed unfavorable risk–benefit when pembrolizumab was added to pomalidomide and dexamethasone ...in patients with relapsed or refractory multiple myeloma (MM). This subgroup analysis reported outcomes in 27 Japanese patients randomly assigned to receive pembrolizumab plus pomalidomide and dexamethasone (
n
= 15) or pomalidomide and dexamethasone alone (
n
= 12). Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). After a median (range) follow-up of 9.6 (1.4–15.3) months in Japanese patients, median PFS 6.5 vs 2.8 months; hazard ratio (HR) 0.16 (95% CI 0.03–0.83) and OS not reached vs 14.8 months; HR 0.46 (95% CI 0.05–4.20) seemed to favor the pembrolizumab plus pomalidomide and dexamethasone arm. Objective response rate was numerically higher in this group (47%) than in the pomalidomide and dexamethasone group (25%). The safety profile was consistent with that of the overall study population. No deaths were attributed to a study drug by the investigators. Although adding pembrolizumab to pomalidomide and dexamethasone did not show unfavorable risk–benefit in the Japanese subgroup of KEYNOTE-183, the analysis is limited by short follow-up and small sample size, which affects the generalizability of the results.
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