Evaluating the long-term effectiveness and safety of nivolumab plus ipilimumab versus nivolumab alone after surgery in patients with stage IV melanoma.

This study evaluated the effectiveness and safety of nivolumab (Opdivo) plus ipilimumab (Yervoy) versus nivolumab alone given after surgery in patients with stage IV melanoma. The data showed that both nivolumab plus ipilimumab and nivolumab alone after surgery were effective compared with placebo and significantly improved survival without cancer recurrence with manageable side effects in these patients.

Melanoma is one of the most aggressive forms of skin cancer. Treatment for melanoma commonly includes surgery to remove the tumor. In some patients, the tumor can come back after surgery (recurrence). In more advanced melanoma, the tumor can spread to other parts of the body (metastasis). In patients with more advanced-stage melanoma, the risk of recurrence or metastasis is higher.

To avoid this, patients can be given additional therapy after surgery (adjuvant treatment). Immunotherapy uses the body’s own system to fight against cancer cells. Tumor cells try to avoid death by switching off our immune system. They bind to proteins on the surface of the immune cells such as PD-1/PD-L1 or CTLA-4. Immunotherapy like nivolumab and ipilimumab block these interactions and turn on the immune system to attack and kill cancer cells. However, the effectiveness and safety of nivolumab plus ipilimumab versus nivolumab alone given after surgery in patients with stage IV melanoma is still unknown.

This study involved 167 patients with stage IV melanoma. Patients were randomly assigned into 3 groups. Group 1 included 56 patients who received nivolumab plus ipilimumab. Group 2 included 59 patients who received nivolumab alone. Group 3 included 52 patients who received a placebo. The average follow-up time was 49.2 months.

After 4 years, 64.2% of the patients in group 1 were alive without cancer recurring compared to 31.4% in group 2 and 15% in group 3. The average survival without cancer recurring was not reached (exceeded the average follow-up period) in group 1 compared to 12.3 months in group 2 and 6.3 months in group 3. Patients in group 1 were 75% more likely to survive without cancer coming back compared to patients in group 3. Patients in group 2 were 40% more likely to survive without cancer coming back compared to patients in group 3.

After 4 years, 83.8% of the patients in group 1 were alive compared to 72.6% in group 2 and 63.1% in group 3. The average overall survival was not reached (exceeded the average follow-up period) in any of the three groups. Patients in group 1 were 59% more likely to have a better overall survival compared to patients in group 3. Patients in group 2 were 25% more likely to have a better overall survival than those in group 3.

71% of the patients in group 1 experienced treatment-related side effects compared to 29% in group 2.

This study concluded that both nivolumab plus ipilimumab and nivolumab alone after surgery were effective compared with placebo and significantly improved survival without cancer recurrence with manageable side effects in patients with stage IV melanoma.

Bristol-Myers Squibb, the manufacturer of nivolumab, funded this study.