Highlights from

ASCO 2021

American Society of Clinical Oncology annual meeting

Virtual 4-8 June 2021

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

Summary: First-line treatment of patients with microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC) with pembrolizumab improves 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 III KEYNOTE 177 trial (NCT02563002), 307 patients with MSI-H/dMMR mCRC who had not previously received treatment were randomly assigned 1:1 to receive pembrolizumab (200 mg Q3W 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 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-1/PD-L1 therapies off-study (60% effective crossover rate in the ITT). 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. Overall survival rate at 3 years follow-up was 61% in the pembrolizumab arm versus 50% in the chemotherapy arm. “Although a statistically significant benefit of pembrolizumab versus chemotherapy could not be observed, probably because of a high cross-over rate, the final results of KENOTE 177 confirm pembrolizumab as a new standard-of-care in the first line for patient with MSI-H/dMMR mCRC,” concluded Prof André.

  1. Le D T, Durham J N et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade. Science 2017;357:409-413 [full text]
  2. André T, Shiu K et al. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med 2020;383:2207-2218 [full text]
  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 2021

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