ASCO: Merck’s Keytruda tops chemo in MSI-H colorectal cancer

Merck & Co/MSD lifted the lid off its data for Keytruda in colorectal cancer patients with a specific biomarker at ASCO, showing that the PD-1 inhibitor more than doubled progression-free survival (PFS) compared to chemotherapy.

The phase 2 study in patients with advanced colorectal cancer who also had microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) mutations showed that patients on Keytruda (pembrolizumab) went 16.5 months without the disease worsening or death, compared to 8.2 months for chemo.

The KEYNOTE-177 trial presented at ASCO yesterday involved patients with advanced cancer that couldn’t be treated with surgery, often because it had spread to other parts of the body, who in many cases would be considered incurable.

Investigators could choose the chemotherapy-based regimen they used as the comparator in the trial, and a number opted for the combination of Roche’s Avastin (bevacizumab) with mFOLFOX6, which is a go-to therapy.

It also revealed that Keytruda cut the risk of disease progression or death by 40% compared to chemo, which is currently the standard treatment for these patients, and 48.3% of the patients on Merck’s drug lived without disease progression for two years, compared with 18.6% of patients on chemotherapy.

Remarkably, 11% of Keytruda-treated patients saw their cancer disappear completely, a result which was seen in just under 4% of the chemotherapy arm.

“These long-awaited trial results will change clinical practice,” commented lead study author Thierry André of Sorbonne University and St Antoine Hospital in an ASCO statement, adding that the study “demonstrates a huge benefit in first line with pembrolizumab and should be the new standard of care”.

MSI-H and dMMR mutations occurs in around 5% and 15% respectively of all colorectal cancer patients, and these tumours are less likely to respond to chemo, meaning patients typically have lower survival rates.

Keytruda is already approved as a treatment for all MSI-H tumours, regardless of where they appear in the body, and with the new first-line data is looking to stay ahead of competition in this area, notably Bristol-Myers Squibb’s Opdivo (nivolumab).

In 2017 Opdivo was approved for MSI-H and dMMR mutated colorectal cancer only, based on the results of the phase 2 CheckMate-142 trial, although that was as a second-line treatment only, and the following year it was also cleared for use in combination with BMS’ CTLA4 inhibitor Yervoy (ipilimumab) in these patients.

BMS is currently testing the combination in the first-line setting too, and also as neoadjuvant (pre-surgery) treatment of MSI-H or dMMR-positive colorectal cancer.