Updated Analysis of Nivolumab Plus Ipilimumab Combos Highlights Long OS for Advanced Melanoma

The 6.5-year updated analysis of the phase 3 CheckMate 067 trial highlighted notable overall survival benefit with nivolumab alone or in combination with ipilimumab for patients with advanced melanoma.

Patients with advanced melanoma experienced durable melanoma-specific survival (MSS) and a long median overall survival (OS) following treatment with nivolumab (Opdivo) alone or in combination with ipilimumab (Yervoy), according to data from the phase 3 CheckMate 067 trial (NCT01844505) published in the Journal of Clinical Oncology.

After a median follow-up of 6.5 months, the median OS was 72.1 months in the nivolumab plus ipilimumab group, 36.9 months in the nivolumab group, and 19.9 months for ipilimumab group. Additionally, the median MSS was not reached, 58.7 months, and 21.9 months in each group, respectively. The 6.5-year OS rate was 57.0%, 43.0%, and 25.0% for patients with BRAF-mutant tumors, and 46.0%, 42.0%, and 22.0% for BRAF wild-type tumors in the combination, nivolumab, and ipilimumab groups, respectively.

A total of 1296 patients enrolled on the study, 314 of whom were randomized to the combination therapy arm, 316 to nivolumab arm, and 315 to ipilimumab arm. Patients recieved 1 mg/kg of nivolumab plus ipilimumab at 3 mg/kg once every 3 weeks for 4 doses then followed by 3 mg/kg of nivolumab once every 2 weeks; 3 mg/kg of nivolumab or ipilimumab once every 3 weeks for 4 doses.

At the time of data cutoff, the median follow-up was 77.0 months, including 57.5 months for the combination group, 36.0 for the nivolumab group, and 18.6 months for the ipilimumab group. Most patients were no longer receiving therapy at the data cutoff, with the exception of 15 patients who continued with treatment.

The median investigator assessed progression-free survival (PFS) was 11.5 months (95% CI, 8.7-19.3) in the combination group, 6.9 months (95% CI, 5.1-10.2) in the nivolumab group, and 2.9 months (95% CI, 2.8-3.2) in the ipilimumab group. Additionally, the 6.5-year PFS rates were 34%, 29%, and 7% in each group, respectively. Additionally, the median OS was 72.1 months (95% CI, 38.2–not reached [NR]) in the combination group, 36.9 months (95% CI, 28.2-58.7) in the nivolumab group, and 19.9 months (95% CI, 16.8-24.6) in the ipilimumab group.

The 6-year PFS rate for those with BRAF-mutant tumors was 34.0% in the combination group, 31.0% in the nivolumab group, and 6.0% in the ipilimumab groups, while those with BRAF-wild type tumors had PFS rates of 46.0%, 42.0%, and 22.0%, respectively. Those with BRAF-mutant tumors had a median OS that was NR in the combination group, 45.5 months in the nivolumab group, and 24.6 months in the ipilimumab group, and 39.1 months, 34.4 months, and 18.5 months for those with BRAF wild-type tumors in each group, respectively.

Investigators also reported 6.5-year OS rates of 49.0%, 42.0%, and 23.0% in each group, respectively.

A post hoc analysis found the median MSS was NR in the combination group, 58.7 months in the nivolumab group, and 21.9 months in the ipilimumab group. Additionally, the 6.5-year MSS rates were 56.0%, 48.0%, and 27.0%, respectively.

Overall, 11 patients died from reasons unrelated to treatment between the 5-year analysis and current cut off. Patients died from progressive melanoma, adenocarcinoma, gallbladder malignancy, and 1 patient had an unknown cause of death.

The overall response rate (ORR) remained unchanged between the analysis at 5 years and the analysis at 6.5 years, with the rates being 58.0% in the combination group, 45.0% in the nivolumab group, and 19.0% in the ipilimumab group. At 77.0 months, the median duration of response was reached in the ipilimumab group alone as 19.2 months.

Progressive disease of the central nervous system was observed in 14 patients in the combination group, 19 in the nivolumab group, and 28 in the ipilimumab group. Between the 2 analyses for data cutoff, 7 patients had progressive disease.

Subsequent therapy was given to 36.0% of the combination group, 49.0% to the nivolumab group, and 66.0% to the ipilimumab group, and the median time from random assignment to the start of subsequent systemic therapy was NR (95% CI, 59.6-NR), 25.2 months (95% CI, 16.0-43.2), and 8.0 months (95% CI, 6.5-8.7), respectively.

Investigators did not determine any new safety signals in the updated analysis.

Reference

Wolchok JD, Chiarion-Sileni V, Gonzalez R, et al. Long-term outcomes with nivolumab plus ipilimumab or nivolumab alone versus ipilimumab in patients with advanced melanoma. J Clin Oncol. 2022;40(2):127-137. doi:10.1200/JCO.21.02229