What is the effective dose of ipilimumab combined with standard dose of pembrolizumab in patients with advanced melanoma?

The study aimed to evaluate the effectiveness and safety of combining standard-dose pembrolizumab (PEM; Keytruda) with two different doses of ipilimumab (IPI; Yervoy) in patients with advanced melanoma. The study concluded that 200 mg PEM plus 50 mg of IPI showed good effectiveness and reduced toxicity compared to 100 mg IPI.

Immunotherapy is a type of cancer treatment that makes use of the immune system to fight cancer. The cancer cell has some proteins present on the surface that help to turn off the immune system by binding proteins on the surface of the immune cells such as PD-1/PD-L1 or CTLA4. Immune checkpoint inhibitors (ICI) such as IPI and PEM block these interactions and turn on the immune system to attack and kill the cancer cells.

Melanoma is one of the most aggressive forms of skin cancer. Recent use of anti-PD-1/L1 (PEM) plus anti-CTLA-4 (IPI) treatment showed effective results in advanced melanoma. However, a standard dose of PD-1/PD-L1 inhibitor (PEM) plus CTLA-4 inhibitor (IPI) beyond a certain dose limit is not well tolerated among these patients. It is important to evaluate which dose of IPI is less toxic in combination with standard-dose PEM for patients with advanced melanoma. 

The study involved 102 patients with advanced melanoma. Patients were randomly assigned to one of 2 groups of 51 patients. Group 1 received four doses of IPI 50 mg every 6 weeks plus 200 mg PEM every 3 weeks. Group 2 received four doses of IPI 100 mg every 12 weeks plus 200 mg PEM every 3 weeks. The treatments lasted for up to 24 months in both groups. The average follow-up for was 16.3-16.4 months.

55% of patients showed a response in group1 compared to 61% in group2. A complete response (complete disappearance of cancer signs) was seen in 16% of group1 compared to 25% in group2. 88% of the patients in group 1 and 91% of group 2 had a reduction in tumors.

After 12 months, 65% of group 1 and 82% of group 2 were alive without disease progression. After 18 months, 85% of patients in group 1 and 82% in group 2 were alive. 

16% of the patients in group 1 and 24% in group 2 stopped treatment due to side effects. The most common side effects in both groups were tiredness, itchy skin, diarrhea, inflammation of the lining of the colon, and increased liver and pancreatic enzymes. Severe side effects were less common in group 1 (24%) compared to group 2 (39%). Immune-related side effects such as low thyroid function and inflammation of the lining of the large intestine were reported in 41% of group 1 and 55% of group 2. 

This study showed that both IPI doses were effective, but IPI 50 mg had fewer side effects when combined with standard-dose PEM in patients with advanced melanoma. 

The study was funded by Merck, the manufacturer of PEM.