Long-Term Data Show Nivolumab May Provide Sustained Benefit Compared With Ipilimumab

CHICAGO—Adjuvant nivolumab provided sustained efficacy among patients with resected stage IIIB/C or IV melanoma at high risk of recurrence compared with ipilimumab, according to an oral presentation at the 2018 American Society of Clinical Oncology Annual Meeting.¹

Previous studies demonstrated that ipilimumab significantly improved recurrence-free survival (RFS), distant metastases-free survival (DMFS), and overall survival compared with placebo in this patient population, but RFS benefits begin to plateau after 3 years. Preliminary findings from CheckMate 238 (ClinicalTrials.gov Identifier: NCT02388906) showed treatment with nivolumab significantly prolonged RFS compared with ipilimumab in patients with resected stage III/IV melanoma after a minimum 18-month follow-up.

For this presentation, study authors reported updated data of 906 patients after 6 months of additional follow-up. Eligible patients were age 15 years or older who had complete resection of stage IIIB/C or IV melanoma. Patients were randomly assigned to either nivolumab 3 mg/kg every 2 weeks (453 patients) or ipilimumab 10 mg/kg every 3 weeks for 4 doses, then every 12 weeks from week 24 (453 patients) for up to 1 year or until disease recurrence or unacceptable toxicity. 

After a minimum of 24 months, the RFS was still significantly longer for nivolumab-treated patients compared with ipilimumab-treated patients (hazard ratio [HR] 0.66; 95% CI, 0.54-0.81; P < .0001), with 171 and 221 events occurring in the nivolumab and ipilimumab arms, respectively.

The RFS rates at month 24 were higher for the nivolumab arm according to subgroups stratified by disease stage III (stage IIIB: 71.0% vs 61.0%; stage IIIC: 58.0% vs 45.0%) and disease stages III and IV (stage III: 64.0% vs 52.0%; stage IV: 58% vs 44%). Subgroup analyses of PD-L1 expression (<5%: 55.2% vs 45.5%; ≥5%: 75.5% vs 58.4%), and BRAF mutation (wild type: 63.5% vs 46.2%; mutant: 61.9% vs 51.7%) also demonstrated sustained RFS benefit after 24 months.

In addition, DMFS remained significantly longer in the nivolumab group compared with the ipilimumab group (70.5% vs 63.7%; HR, 0.76; 95% CI, 0.59-0.98; P = .034). A fewer proportion of nivolumab-treated patients (31.5%) required subsequent therapy versus patients in the ipilimumab group (41.1%). 

Overall, longer follow-up data indicated a significant and lasting efficacy benefit with adjuvant nivolumab compared with ipilimumab in this patient group who were at high risk of recurrent disease. The authors concluded that “these more mature data continue to demonstrate durable clinical benefit with nivolumab and further support its use for resected stage III and IV melanoma.”

Read more of Cancer Therapy Advisor‘s coverage of the American Society of Clinical Oncology (ASCO) 2018 meeting by visiting the conference page.

Reference

1. Weber JS, Mandala M, Del Vecchio M, et al.  Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: Updated results from a phase III trial (CheckMate 238). Oral presentation at the American Society of Clinical Oncology 2018 Meeting; June 1-5, 2018; Chicago, IL.