Pembrolizumab as a treatment for advanced colorectal cancer predisposed to mutations.

This study compared the use of pembrolizumab (Keytruda) to chemotherapy for the treatment of patients with colorectal cancer (CRC) and high microsatellite instability (MI). This study showed that patients who received pembrolizumab had a better outcome than those who were given chemotherapy.

Patients who are diagnosed with CRC that has spread to other areas (metastatic) are treated with chemotherapy. There is a subtype of CRC that has a lot of specific genetic changes (mutations). These tumors have high MI. High MI CRC is less sensitive to chemotherapy. Patients with high MI CRC often relapse (the disease returns/progresses) or are refractory (do not respond) to treatment. Other treatment options are being explored for these patients, such as immunotherapy.

Pembrolizumab is one immunotherapy that allows the immune system to target and kill cancer cells. It is not yet clear how safe and effective pembrolizumab is in the treatment of patients with high MI CRC.

This study includes 307 patients with high MI CRC. 153 patients randomly received pembrolizumab and 154 were given chemotherapy. Patients who did not respond to chemotherapy could cross over to the pembrolizumab group. The average follow-up time was 32.4 months.

43.8% of patients in the pembrolizumab group responded to therapy. 33.1% of patients in the chemotherapy showed a response. 83% of the patients in the pembrolizumab showed had a continued response after 24 months. This was compared to 35% in the chemotherapy group.

The average time patients had no disease progression was significantly longer in the pembrolizumab group compared to the chemotherapy group (16.5 months vs 8.2 months). 48.3 % of patients in the pembrolizumab group survived without worsening of their disease at 24 months compared to 18.6% of patients in the chemotherapy group.

Serious side effects were seen in 56% of the pembrolizumab group and 78% of the chemotherapy group.

This study found that patients with high MI CRC who were treated with pembrolizumab had a better response and fewer side effects compared to those treated with chemotherapy.

Overall survival of the patients in the study has not yet been reported. The analysis did not allow for a comparison between groups because a significant number of patients in the chemotherapy group crossed over to the pembrolizumab group. The study was funded by Merck Sharp and Dohme who manufacture pembrolizumab.