Treating advanced melanoma with pembrolizumab plus reduced-dose ipilimumab.

This study was carried out to determine whether combination therapy with a standard-dose pembrolizumab (Keytruda) plus reduced-dose ipilimumab (Yervoy) could be used as a treatment option in patients with advanced melanoma. The study found that this combination had good outcomes and manageable side effects in these patients.

Melanoma is a form of skin cancer that develops from color cells in the skin called melanocytes. Melanoma is the most dangerous form of skin cancer worldwide. Many cancer cells have on their surface proteins or receptors that lower the sensitivity of the immune system. This makes it difficult for the immune system to fight the cancer and leads to tumor growth.

PD-L1-is a type of cell receptor that has a role in immune regulation. Pembrolizumab is an antibody (a y-shaped protein that has a role in the immune system) that targets PD-L1 in melanoma cells. Pembrolizumab is the standard treatment option for melanoma. Ipilimumab is also an antibody that targets CTLA-4 (protein receptor that is involved in shutting down the immune system).

Pembrolizumab and ipilimumab have shown significant effectiveness in melanoma. However, this combination has also been associated with significant side effects. The effectiveness and safety of standard-dose pembrolizumab combined with reduced-dose ipilimumab in patients with advanced melanoma remain unclear. 

There were 153 patients with advanced melanoma in this trial. Patients received standard-dose pembrolizumab (2mg/kg once every 3 weeks) with reduced-dose ipilimumab (1mg/kg every 3 weeks) for 4 cycles. This was followed up with pembrolizumab alone for 2 years or until disease progression. The average follow-up was 36.8 months.

Overall, 69.3% of the patients stopped treatment early due to side effects, disease progression, or lack of respecting the trial conditions. 47.1% of patients experienced severe side-effects. 35.9% of patients stopped treatment due to intolerable side effects. The most common side effects were fatigue, skin rash, itching, diarrhea, and discoloration of the skin. The most common severe side effects were increased liver enzymes, and inflammation of the liver and colon. 

The objective response rate (ORR) was 62.1% overall. 27.5% of patients achieved a complete response (CR; no signs of cancer). 34.6% of patients reached a partial response (PR; tumor shrinkage). Of the 127 patients with PD-L1-positive tumors, 26.8% had a CR and 38.6% had a PR. Of the 24 patients with PD-L1-negative tumors, 33.3% had a CR and 16.7% had a PR.

Of 140 patients with an image assessment of the tumor before treatment, 82.8% experienced a reduction in tumor size. The average time to tumor response was 2.8 months. Three-year survival without cancer worsening was estimated at 59.1%. Three-year overall survival (OS) was 73.4%.

The authors concluded that using a standard dose of pembrolizumab plus a reduced dose ipilimumab had good antitumor activity, and long term survival, with manageable side effects. 

This study was funded by Merch Sharp & Dohme Corp, the manufacturer of pembrolizumab.