Abstract
BackgroundNivolumab (an anti–programmed death-1 antibody) is an adjuvant standard of care for patients with high-risk resected melanoma, although a watch-and-wait strategy remains an option. In the absence of head-to-head evidence, an indirect treatment comparison (ITC) of adjuvant nivolumab versus placebo, the proxy for a watch-and-wait strategy, was conducted in patients with high-risk resected melanoma. MethodsAn ITC using the Bucher method compared nivolumab with placebo using intention-to-treat population data from the phase III CheckMate 238 (nivolumab vs ipilimumab; minimum follow-up, 4 years; NCT02388906) and European Organisation for Research and Treatment of Cancer (EORTC) 18071 (ipilimumab vs placebo; minimum follow-up, ≈4.5 years; NCT00636168) trials. The end-points were recurrence-free survival (RFS), distant metastasis-free survival (DMFS) and overall survival (OS). To account for cross-trial differences in staging and subsequent therapy, additional analyses examined patients with stage IIIB/IIIC disease and adjusted post-recurrence survival in EORTC 18071, respectively. ResultsNivolumab versus placebo was associated with clinically meaningful improvements in RFS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.42–0.68) and OS (HR, 0.63; 95% CI, 0.45–0.89). Nivolumab versus placebo was also associated with clinically meaningful improvements in RFS (HR, 0.53; 95% CI, 0.40–0.69), DMFS (HR, 0.62; 95% CI, 0.46–0.83) and OS (HR, 0.67; 95% CI, 0.47–0.97) in patients with stage IIIB/IIIC disease and in OS (HR, 0.65; 95% CI, 0.46–0.92) in the overall population after adjusting post-recurrence survival in EORTC 18071. ConclusionThis ITC shows that adjuvant nivolumab provides clinically meaningful improvements in RFS, DMFS and OS versus a watch-and-wait strategy in high-risk resected melanoma.
Highlights
Patients with locally advanced melanoma are at high risk of disease recurrence, disease progression, or death even after complete surgical resection, and systemic adjuvant treatment can help eradicate residual micrometastatic disease in these patients [1]
High-dose interferon and the antiecytotoxic T lymphocyte antigen-4 (CTLA-4) antibody ipilimumab are approved as adjuvant therapy but are no longer recommended as routine treatments [2]
Similar improvements in overall survival (OS) with nivolumab versus placebo in EORTC 18071 were noted with the other post-recurrence survival increases (63% in the ipilimumab arm and 53%, 73% and 83% in the placebo arm; Table 4). Results of this indirect treatment comparison (ITC) show that adjuvant nivolumab is associated with clinically meaningful improvements in recurrence-free survival (RFS), distant metastasisfree survival (DMFS) and OS versus placebo, the proxy for a watch-and-wait strategy, in patients with high-risk resected melanoma
Summary
Patients with locally advanced (stage III/IV) melanoma are at high risk of disease recurrence, disease progression, or death even after complete surgical resection, and systemic adjuvant treatment can help eradicate residual micrometastatic disease in these patients [1]. The antieprogrammed death (PD)-1 antibodies nivolumab and pembrolizumab, as well as the BRAF/MEK inhibitor combination of dabrafenib plus trametinib (for patients with the BRAF V600 mutation), are considered standardof-care adjuvant treatments for patients with high-risk resected melanoma [2]. Ipilimumab, pembrolizumab and dabrafenib plus trametinib have been compared with placebo, the proxy for a watch-and-wait strategy, as adjuvant treatment in phase III randomised controlled trials (RCTs) and shown to have significant benefits [3e6]. There are no head-to-head studies comparing adjuvant nivolumab with placebo in patients with highrisk resected melanoma
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