Pembrolizumab for previously treated, microsatellite instability–high/mismatch repair–deficient advanced colorectal cancer: final analysis of KEYNOTE-164

Dung T. Le*, Luis A. Diaz, Tae Won Kim, Eric Van Cutsem, Ravit Geva, Dirk Jäger, Hiroki Hara, Matthew Burge, Bert H. O'Neil, Petr Kavan, Takayuki Yoshino, Rosine Guimbaud, Hiroya Taniguchi, Elena Élez, Salah Eddin Al-Batran, Patrick M. Boland, Yi Cui, Pierre Leconte, Patricia Marinello, Thierry André

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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:,

Original languageEnglish
Pages (from-to)185-195
Number of pages11
JournalEuropean Journal of Cancer
StatePublished - Jun 2023
Externally publishedYes


FundersFunder number
Merck Sharp and Dohme


    • Colorectal cancer
    • Microsatellite instability
    • Mismatch repair
    • Pembrolizumab


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