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Adjuvant ipilimumab versus placebo after complete resection of stage III melanoma: long-term follow-up results of the European Organisation for Research and Treatment of Cancer 18071 double-blind phase 3 randomised trial

Published:August 07, 2019DOI:https://doi.org/10.1016/j.ejca.2019.07.001

      Highlights

      • Adjuvant therapy with ipilimumab significantly improved the outcomes.
      • Compared with placebo, it prolonged RFS (hazard ratio [HR], 0.75), DMFS (HR, 0.76) and (OS; HR, 0.73).
      • The estimated absolute increase in the 7-year OS rate was 8.7%.
      • The benefit was sustained long term and consistent across subgroups.

      Abstract

      Background

      Since 2015, adjuvant therapy with ipilimumab is an approved treatment for stage III melanoma based on a significantly prolonged recurrence-free survival (RFS). At a median follow-up of 5.3 years, RFS, distant metastasis-free survival (DMFS) and overall survival (OS) were each significantly prolonged in the ipilimumab group compared with the placebo group, despite a 53.3% (ipilimumab) versus 4.6% (placebo) treatment discontinuation rate due to adverse events. We present now long-term follow-up results of this European Organisation for Research and Treatment of Cancer 18071 trial.

      Patients, methods and results

      A total of 99 sites randomised 951 patients with stage III cutaneous melanoma (excluding lymph node metastasis ≤1 mm or in-transit metastasis) with adequate resection of lymph nodes to receive intravenous infusions of ipilimumab 10 mg/kg or placebo, every 3 weeks for 4 doses, then every 3 months for up to 3 years. The RFS, DMFS and OS, as reported by the local investigators, were assessed by the intention-to-treat analysis. Among 431 patients randomised at 63 sites and who were still alive at the analysis reported in 2016, recent follow-up information could be obtained for 264 patients. The median OS follow-up was 6.9 years. The RFS (hazard ratio [HR] 0.75, 95% confidence interval 0.63–0.88; P < 0.001), DMFS (HR 0.76, 0.64–0.90; P = 0.002) and OS (HR 0.73, 0.60–0.89; P = 0.002) benefit observed in the ipilimumab group was durable with an 8.7% absolute difference at 7 years for OS. The benefit was consistent across subgroups.

      Conclusions

      Adjuvant therapy with ipilimumab prolongs RFS, DMFS and OS significantly. The benefit is sustained long term and consistent across subgroups.

      Keywords

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