CheckMate 067 Shows OS Improved With Nivolumab/Ipilimumab in Melanoma

A nivolumab/ipilimumab combination and nivolumab alone significantly improved overall survival (OS) compared with ipilimumab alone for advanced melanoma patients, according to a new study. In addition, in descriptive analyses, the combination appeared to provide favorable survival outcomes over nivolumab alone, including across clinically relevant subgroups.

Previously, nivolumab plus ipilimumab had improved progression-free survival (PFS) and objective response rate (ORR) vs ipilimumab alone in the phase II CheckMate 069 and phase III CheckMate 067 trials of treatment-naive patients with advanced melanoma.

These data were presented at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC.

“Updated results from the CheckMate 067 trial confirm the PFS data. The OS data are consistent with that seen in PFS, with no new safety concerns,” study coauthor F. Stephen Hodi, MD, professor of medicine at Harvard Medical School in Boston, told Cancer Network.

Hodi noted that the OS data are not yet mature and need longer follow-up. He also noted that the CheckMate 067 trial was not powered to make the comparison of nivolumab plus ipilimumab vs nivolumab alone.

CheckMate 067 enrolled 945 patients with advanced melanoma who had not received prior treatment for advanced disease. Patients were randomly assigned 1:1:1 to nivolumab plus ipilimumab, nivolumab, or ipilimumab. They received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for 4 doses followed by nivolumab 3 mg/kg every 2 weeks, nivolumab 3 mg/kg every 2 weeks plus placebo, or ipilimumab 3 mg/kg every 3 weeks for 4 doses plus placebo, until progression or unacceptable toxicity.

After a minimum follow-up of 28 months, median OS among those patients randomly assigned ipilimumab was 20 months. The median OS had not been reached for the nivolumab plus ipilimumab or the nivolumab plus placebo arms.

Two-year OS rates were highest among those randomly assigned nivolumab plus ipilimumab (64%) compared with those randomly assigned to nivolumab plus placebo (59%) and ipilimumab alone (45%).

A similar trend was seen for median duration of response. Median duration of response had not been reached in the nivolumab plus ipilimumab arm; it was 31.1 months and 18.2 months for the nivolumab plus placebo arm and ipilimumab-alone arm, respectively.

In descriptive analyses, patients randomly assigned nivolumab plus ipilimumab had a 12% lower risk of death compared with those randomly assigned nivolumab plus placebo.

As in previous reports, the frequency of grade 3/4 adverse events was higher among those randomly assigned nivolumab plus ipilimumab (58%) compared with those randomly assigned nivolumab plus placebo (21%) or ipilimumab alone (28%). The most common side effects in the combination group were diarrhea/colitis and hepatitis, which were generally manageable.

In patients with tumor programmed death ligand 1 (PD-L1) expression ≥ 5%, the 2-year OS rate was higher in the nivolumab arm (72%) than the combination (68%); it was 54% with ipilimumab. “This shows the robustness of PD-L1 positivity as a potential biomarker,” said Hodi.

Hodi noted that the combination of nivolumab plus ipilimumab is used regularly. “Due to durability and response rate for immune therapy, many patients get immune therapy upfront, regardless of their BRAF status. Right now, this is our frontline go-to treatment,” he said.