Pembrolizumab benefits survival in MSI-H/dMMR metastastic colorectal cancer

First-line treatment of patients with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) with pembrolizumab improved overall survival, but the prespecified threshold for significance was not reached. These were the final results of the phase 3 KEYNOTE 177 trial.

Immune checkpoint blockade has a predicted clinical benefit in patients with MSI-H/dMMR mCRC [1]. In the phase 3 KEYNOTE 177 trial (NCT02563002), 307 treatment-naïve patients with MSI-H/dMMR mCRC were randomly assigned 1:1 to receive pembrolizumab (200 mg every 3 weeks up to 35 cycles) or chemotherapy every 2 weeks. Results from an interim analysis showed significant prolonged progression-free survival in patients treated with pembrolizumab versus chemotherapy (median 16.6 months vs 8.2 months) [2]. Prof. Thierry André (Sorbonne University, France) presented the final results of KEYNOTE 177, after 190 overall survival events [3].

The median study follow-up was 44.5 months in the pembrolizumab arm versus 44.4 months in the chemotherapy arm. In the chemotherapy arm, 56 (36%) patients crossed over to pembrolizumab, with 37 more receiving anti-PD-(L)1 therapies off-study (60% effective crossover rate in the intention-to-treat population). Median overall survival was not reached in the pembrolizumab arm versus 36.7 months in the chemotherapy arm. The hazard ratio for overall survival favoured pembrolizumab versus chemotherapy with a trend toward reduction in the risk of death (HR 0.74). However, this difference did not reach prespecified statistical significance. At 3 years, the overall survival rate was 61% in the pembrolizumab arm versus 50% in the chemotherapy arm.

1. Le DT, et al. Science 2017;357:409-413.
2. André T, et al. N Engl J Med. 2020;383:2207-2218.
3. André T, et al. Final overall survival for the phase III KN177 study: Pembrolizumab versus chemotherapy in microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). Abstract 3500, ASCO 2021 Virtual Meeting, 4–8 June.

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Posted on 12 August 202117 May 2024