Pembrolizumab for previously treated, microsatellite instability–high/mismatch repair–deficient advanced colorectal cancer: Final analysis of KEYNOTE-164 Journal Article
| Authors: | Le, D. T.; Diaz, L. A. Jr; Kim, T. W.; Van Cutsem, E.; Geva, R.; Jäger, D.; Hara, H.; Burge, M.; O'Neil, B. H.; Kavan, P.; Yoshino, T.; Guimbaud, R.; Taniguchi, H.; Élez, E.; Al-Batran, S. E.; Boland, P. M.; Cui, Y.; Leconte, P.; Marinello, P.; André, T. |
| Article Title: | Pembrolizumab for previously treated, microsatellite instability–high/mismatch repair–deficient advanced colorectal cancer: Final analysis of KEYNOTE-164 |
| Abstract: | Background: Pembrolizumab demonstrated durable clinical benefit and manageable safety in previously treated advanced or metastatic microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) colorectal cancer (CRC) in the phase 2 KEYNOTE-164 study. Results from the final analysis are presented. Methods: Eligible patients had unresectable or metastatic MSI-H/dMMR CRC and ≥2 prior systemic therapies (cohort A) or ≥1 prior systemic therapy (cohort B). Patients received pembrolizumab 200 mg intravenously every 3 weeks for ≤35 cycles. The primary end-point was objective response rate (ORR) assessed per Response Evaluation Criteria in Solid Tumors, version 1.1 by blinded independent central review. Secondary end-points included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety and tolerability. Results: Sixty-one patients in cohort A and 63 patients in cohort B were enroled; median follow-up was 62.2 months and 54.4 months, respectively. ORR was 32.8% (95% CI, 21.3%–46.0%) in cohort A and 34.9% (95% CI, 23.3%–48.0%) in cohort B. Median DOR was not reached (NR) in either cohort. Median PFS was 2.3 months (95% CI, 2.1–8.1) in cohort A and 4.1 months (95% CI, 2.1–18.9) in cohort B. Median OS was 31.4 months (95% CI, 21.4–58.0) in cohort A and 47.0 months (95% CI, 19.2–NR) in cohort B. No new safety signals were observed. Nine patients who initially responded experienced disease progression off therapy and received second-course pembrolizumab. Six patients (66.7%) completed an additional 17 cycles of pembrolizumab, and 2 patients achieved a partial response. Conclusions: Pembrolizumab continued to show durable antitumor activity, prolonged OS, and manageable safety in patients with previously treated MSI-H/dMMR CRC. Clinical Trial Registry Information: ClinicalTrials.gov, NCT02460198 © 2023 |
| Keywords: | adult; cancer survival; treatment response; middle aged; major clinical study; overall survival; genetics; drug tolerability; fatigue; hepatitis; advanced cancer; cancer growth; drug efficacy; drug safety; drug withdrawal; side effect; systemic therapy; unspecified side effect; skin manifestation; follow up; colorectal cancer; progression free survival; multiple cycle treatment; colonic neoplasms; cohort analysis; pneumonia; colorectal neoplasms; alanine aminotransferase; survival time; colorectal tumor; mismatch repair; colon tumor; microsatellite instability; dna mismatch repair; pancreatitis; colitis; hyperthyroidism; hypothyroidism; triacylglycerol lipase blood level; sarcoidosis; turcot syndrome; triacylglycerol lipase; phase 2 clinical trial (topic); metastatic colorectal cancer; myositis; vasculitis; response evaluation criteria in solid tumors; infusion related reaction; humans; human; male; female; article; pembrolizumab; patient history of therapy; alanine aminotransferase level |
| Journal Title: | European Journal of Cancer |
| Volume: | 186 |
| ISSN: | 0959-8049 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2023-06-01 |
| Start Page: | 185 |
| End Page: | 195 |
| Language: | English |
| DOI: | 10.1016/j.ejca.2023.02.016 |
| PUBMED: | 37141828 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2023 -- Source: Scopus |
