Comparison of pembrolizumab with chemotherapy in ipilimumab-resistant melanoma

The authors compared the safety and effectiveness of pembrolizumab (Keytruda) to chemotherapy for the treatment of ipilimumab (Yervoy)-resistant melanoma. 

Ipilimumab, an immunotherapy (treatment that uses the body’s own immune system to fight cancer), is an approved drug for the treatment of advanced melanoma (stage III/ IV). In 40-50% of melanoma patients, BRAF genes are mutated (permanently changed). These genes are important in cell signaling. BRAF inhibitors are one of the standard treatments used in these patients. These drugs stop certain cell signaling proteins used by melanoma cells containing mutated BRAF genes. However, when disease progresses despite ipilimumab and BRAF inhibitor treatment, chemotherapy becomes the only option, wherever applicable. Pembrolizumab is another immunotherapy. This works by inhibiting PD-1, an important protein in the immune system. This inhibition triggers the immune system to attack tumor cells.

Understanding the treatment outcomes of pembrolizumab is valuable for determining alternative therapies in melanoma.

The authors aimed to compare the safety and effectiveness of pembrolizumab to chemotherapy in melanoma patients.

540 patients were included in this study. All patients had advanced melanoma that could not be surgically removed. All patients had previously received 2 or more doses of ipilimumab. In addition, those who had BRAF mutations received BRAF inhibitors. All patients had progressive disease within 24 weeks of treatment. In group 1,180 patients received 2 mg/kg of pembrolizumab. In group 2, 181 patients received 10 mg/kg of pembrolizumab. In group 3, 179 patients received standard chemotherapy.

There was a 43% reduced risk of disease progression in group 1 compared to group 3. There was a 50% reduced risk of disease progression in group 2 compared to group 3. At 6 months, progression free survival (time following treatment before the disease progressed) was 34% in group 1, 38% in group 2 and 16% in group 3.

Serious (grade 3) or life-threatening (grade 4) treatment-related side effects affected 11% in group 1, 14% in group 2 and 26% in group 3. The most common side effect in the pembrolizumab group was fatigue. 2 patients in group 1 and 1 patient in group 2 were affected by fatigue. This was compared to 8 patients in group 3. In group 2 other side effects included swelling and muscle pain. In group 3 other side effects included inflammation of the colon, loss of appetite, diarrhea and hypopituitarism. Hypopituitarism is the lack of hormone secretion from pituitary gland located in the brain. Apart from fatigue, the most common side effects in group 3 were low red and white blood cell counts.

The authors concluded that pembrolizumab could be a safe and effective standard treatment in patients who experience melanoma progression on ipilimumab and other therapies.

If you have a progressive melanoma despite being previously treated with ipilimumab and BRAF inhibitors, talk to your doctor about pembrolizumab.