Europe approves KEYTRUDA® as first-line therapy in certain colorectal cancers

The European Commission approval makes KEYTRUDA® (pembrolizumab) the first anti-PD-1 therapy approved for metastatic microsatellite instability-high (MSI-H) colorectal cancer patients in Europe.

colorectal cancer

The European Commission (EC) has approved KEYTRUDA, Merck/MSD’s anti-PD-1 therapy, as a monotherapy for the first-line treatment of adult patients with metastatic microsatellite instability-high (MSI-H), or mismatch repair deficient (dMMR), colorectal cancer. This approval marks the first gastrointestinal indication for KEYTRUDA in Europe and makes it the first anti-PD-1/L1 therapy approved in Europe for these patients.

The approval is based on results from the Phase III KEYNOTE-177 trial, in which KEYTRUDA monotherapy significantly reduced the risk of disease progression or death by 40 percent, compared with chemotherapy. The treatment also more than doubled median progression-free survival (PFS) compared with chemotherapy (16.5 months versus 8.2 months). In addition, there was a lower incidence of Grade 3 or higher treatment-related adverse events (TRAEs) with KEYTRUDA compared with chemotherapy (22 percent versus 66 percent), and no new toxicities were observed. 

“Before the KEYNOTE-177 trial, conventional chemotherapy with targeted therapy was the standard of care for patients with metastatic colorectal cancer who have tumours that are MSI-H/dMMR,” explained Dr Thierry Andre, professor of medical oncology at Sorbonne University and head of the medical oncology department at St. Antoine Hospital, Assistance Publique Hôpitaux de Paris, both French. “With this approval, patients with metastatic colorectal cancer that is MSI-H or dMMR status will gain a monotherapy treatment option that has shown superior progression-free survival compared to standard of care chemotherapy.”

The approval allows marketing of KEYTRUDA monotherapy in all 27 European Union (EU) member states plus Iceland, Lichtenstein, Norway and Northern Ireland. Following Brexit this approval is also valid in Great Britain.

About the KEYNOTE-177 trial

KEYNOTE-177 was a multi-centre, randomised, open-label, active-controlled trial that enrolled 307 patients with previously untreated metastatic MSI-H or dMMR colorectal cancer. Patients with autoimmune disease or a medical condition that required immunosuppression were ineligible.

Patients were randomized 1:1 to receive KEYTRUDA (200 mg intravenously) every three weeks or investigator’s choice of the following chemotherapy regimens given intravenously every two weeks.

Treatment with KEYTRUDA or chemotherapy continued until the disease progressed or patients experienced unacceptable toxicity. Those treated with KEYTRUDA without disease progression could be treated for up to 24 months. Patients randomised to chemotherapy were offered KEYTRUDA at the time of disease progression. The main efficacy outcome measures were PFS and overall survival (OS). Additional efficacy outcome measures were objective response rate (ORR) and duration of response (DOR).

Additional results:

  • For patients treated with KEYTRUDA, the ORR was 44 percent, with a complete response rate of 11 percent and a partial response rate of 33 percent. The ORR of those on chemotherapy was 33 percent, with a complete response rate of four percent and a partial response rate of 29 percent.
  • Median DOR was not reached with KEYTRUDA versus 10.6 months with chemotherapy. Based on 67 patients with a response in the KEYTRUDA arm and 51 patients with a response in the chemotherapy arm, 85 percent in the KEYTRUDA arm had a DOR greater than or equal to 12 months versus 44 percent in the chemotherapy arm.

About microsatellite instability-high (MSI-H)

MSI is a change that occurs in the DNA of certain cells, such as tumour cells, in which the number of short, repeated sequences of DNA called microsatellite repeats is different from the number of repeats that was in the DNA when it was inherited. The cause of MSI may be a defect in the ability to repair mistakes made when DNA is copied in the cell known as mismatch repair deficiency (dMMR).

About colorectal cancer in Europe

Colorectal cancer is the third most commonly diagnosed cancer and the second most common cause of cancer-related death worldwide. Worldwide, it is estimated there were more than 1,930,000 new cases of colorectal cancer in 2020, with nearly 520,000 occurring in Europe. It is estimated approximately up to 20 percent of colorectal cancer patients have tumours that are MSI-H or dMMR.