CheckMate 037: Nivolumab Improved Responses, Not Survival in Advanced Melanoma

Patients with advanced melanoma treated with nivolumab had higher and more durable responses compared with investigator’s choice of chemotherapy, but these increases did not result in improved survival outcomes, according to the results of the CheckMate 037 study published in the Journal of Clinical Oncology.

“The overall survival outcome may have been impacted by the increased dropout rate before treatment and increased systemic therapy received after assigned therapy in the investigator’s choice of chemotherapy group, as well as an increased proportion of patients with poor prognostic factors in the nivolumab group,” wrote James Larkin, PhD, FRCP, of Royal Marsden NHS Foundation Trust, United Kingdom, and colleagues. “Despite the lack of survival advantage, nivolumab remains an effective option for PD-1 inhibitor–naive patients who experienced failure with ipilimumab and a BRAF inhibitor if BRAF mutated.”

According to Larkin and colleagues treatment options were needed for patients with advanced melanoma that had progressed with ipilimumab and BRAF inhibitor-based therapy. The PD-1 inhibitor nivolumab had shown increased efficacy in metastatic melanoma compared with ipilimumab.

The trial randomly assigned patients 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator’s choice of chemotherapy (dacarbazine or carboplatin/paclitaxel).

More patients in the investigator’s choice group did not receive treatment compared with patients assigned to nivolumab (23% vs 2%). In addition, more patients assigned nivolumab had brain metastases (20% vs 14%) and increased lactate dehydrogenase levels (52% vs 38%). Forty-one percent of patients in the investigator’s choice arm received anti–PD-1 agents after therapy assignment compared with 11% of patients in the nivolumab arm.

With a median follow-up of about 2 years, the median overall survival was 15.7 months for nivolumab compared with 14.4 months for the investigator’s choice arm. Similarly, there was no significant difference in progression-free survival between the two arms.

Patients assigned to nivolumab had a higher overall response rate (27% vs 10%) and a longer median duration of response (32 vs 13 months) compared with the investigator’s choice arm.

The standard of care treatment for melanoma has evolved since the trial started. Anti–PD-1 monotherapy or in combination with anti–CTLA-4 comprise first-line options, “making first-line ipilimumab monotherapy obsolete,” the authors noted.

“Although there were no survival differences between nivolumab and investigator choice chemotherapy treatments, nivolumab treatment after progression on ipilimumab with or without a BRAF inhibitor does provide a higher rate of response and more durable responses,” the researchers wrote. “Some situations may still exist that necessitate the use of ipilimumab as first-line therapy and nivolumab provides a safer option with a better maintained quality of life for patients who have experienced failure with prior systemic therapies compared with cytotoxic chemotherapy.”