Highlights
- •KEYNOTE-164 evaluated pembro in MSI-H/dMMR unresectable/metastatic colorectal cancer (72/85).
- •Additional responses were observed, and median DOR was still NR (72/85).
- •Second-course pembro showed some benefit in patients with progressive disease after initial response (85/85).
- •OS was lengthy for a population with previously treated CRC (75/85).
- •Pembro continued to be well tolerated, and no new safety signals were observed (80/85).
Abstract
Background
Pembrolizumab demonstrated durable clinical benefit and manageable safety in previously
treated advanced or metastatic high microsatellite instability (MSI-H)/DNA mismatch
repair (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
Keywords
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Article info
Publication history
Published online: February 24, 2023
Accepted:
February 16,
2023
Received:
December 21,
2022
Publication stage
In Press Uncorrected ProofIdentification
Copyright
© 2023 Published by Elsevier Ltd.
