European Union: Keytruda, an anti-PD-1 therapy, approved for metastatic microsatellite instability-high colorectal cancer patients
The European Commission ( EC ) has approved Keytruda ( Pembrolizumab ), an 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 European Union 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 Pembrolizumab monotherapy has significantly reduced the risk of disease progression or death by 40%, 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% versus 66% ), and no new toxicities were observed.
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 Pembrolizumab ( 200 mg intravenously ) every three weeks or investigator’s choice of chemotherapy given intravenously every two weeks.
Treatment with Pembrolizumab or chemotherapy continued until the disease progressed or patients experienced unacceptable toxicity.
Those treated with Pembrolizumab without disease progression could be treated for up to 24 months.
Patients randomised to chemotherapy were offered Pembrolizumab at the time of disease progression.
The main efficacy outcome measures were progression-free survival and overall survival ( OS ). Additional efficacy outcome measures were objective response rate ( ORR ) and duration of response ( DOR ).
For patients treated with Pembrolizumab, the ORR was 44%, with a complete response rate of 11% and a partial response rate of 33%.
The ORR of those on chemotherapy was 33%, with a complete response rate of 4% and a partial response rate of 29%.
Median DOR was not reached with Pembrolizumab versus 10.6 months with chemotherapy. Based on 67 patients with a response in the Pembrolizumab arm and 51 patients with a response in the chemotherapy arm, 85% in the Pembrolizumab arm had a DOR greater than or equal to 12 months versus 44% in the chemotherapy arm.
Microsatellite instability-high ( MSI-H ) 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 ).
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% of colorectal cancer patients have tumours that are MSI-H or dMMR. ( Xagena )
Source: Merck ( MSD ), 2021