Overall survival associated with Pembrolizumab (Keytruda) vs. Chemotherapy in MSI-H/dMMR mCRC
The KEYNOTE-177 trial is a landmark study in colorectal cancer treatment that evaluated the efficacy and safety of the immunotherapy drug, pembrolizumab (Keytruda), compared to standard of care chemotherapy for patients with microsatellite instability high (MSI-H), mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) as first-line (initial) treatment. Keytruda led to significantly longer progression-free survival than chemotherapy as a first-line treatment for MSI-H/dMMR mCRC, with fewer treatment-related adverse events. These study findings are what led to the Food and Drug Administration (FDA) and Health Canada approvals of pembrolizumab in this setting.
Progression-free survival (PFS): the amount of time during and after treatment of a disease, such as cancer, that a patients lives with the disease but it does not worsen (National Cancer Institute)
As part of the long-term follow-up of the KEYNOTE-177 study, the researchers aimed to understand the impact of Keytruda on the overall survival of patients in this cohort of mCRC.
Overall survival (OS): the length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive.
Between February 2016 and February 2018, 307 patients were randomly assigned to pembrolizumab or chemotherapy. 60% of patients crossed over from chemotherapy to pembrolizumab during the study. At the final study analysis, average progression-free survival was 16.5 months for pembrolizumab versus 8.2 months with chemotherapy. Pembrolizumab was not shown to be superior to chemotherapy for overall survival, as the findings were not statistically significant. Treatment-related adverse events of grade 3 or worse happened in 22% of patients in the pembrolizumab group compared to 66% of patients in the chemotherapy group.
Take away message:
In the final study analysis, though pembrolizumab showed robust antitumour activity and fewer treatment-related adverse events compared to chemotherapy, there was no significant difference in overall survival between the two treatment groups. These final study findings continue to support pembrolizumab as an effective first-line therapy in patients with MSI-H/dMMR mCRC.