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In the phase II/III RELATIVITY-047 trial, a novel fixed-dose combination (FDC) of nivolumab plus relatlimab (NIVO + RELA; a programmed death-1 and a lymphocyte-activation gene 3 inhibitor, respectively) significantly improved progression-free survival (PFS) versus NIVO in patients with previously untreated unresectable or metastatic melanoma (median follow-up, 13.2 months) with stable health-related quality of life (HRQoL), although grade three or four treatment-related adverse events (TRAEs) were more frequent with the combination. Updated HRQoL results (median follow-up, 19.3 months) are presented. Patients were randomised to receive intravenous NIVO + RELA (480 mg and 160 mg, respectively) or NIVO (480 mg) every 4 weeks. HRQoL was assessed using the Functional Assessment of Cancer Treatment-Melanoma (FACT-M) and EQ-5D-3L questionnaires at baseline, before dosing at each treatment cycle, and at follow-up (posttreatment) visits. Consistent with the initial analysis, HRQoL remained stable with NIVO + RELA on treatment and was similar to that with NIVO. Mean changes from baseline did not exceed clinically meaningful thresholds. HRQoL results were consistent across instruments and scales/subscales. Despite an increased rate of grade three or four TRAEs with NIVO + RELA versus NIVO, the proportion of patients reporting that they were bothered 'quite a bit' or 'very much' by TRAEs was low and comparable between treatments. Results from the RELATIVITY-047 trial show that the PFS benefit with NIVO + RELA FDC over NIVO was obtained with stable patient-reported HRQoL, supporting NIVO + RELA as a first-line treatment option for patients with advanced melanoma. • Nivolumab plus relatlimab (NIVO + RELA) improves PFS versus nivolumab in melanoma, with added toxicity. • In RELATIVITY-047, quality of life (QoL) was stable/similar with both treatments. • Results were consistent across all QoL instruments and subscales. • QoL results suggest that the two treatments had similar overall tolerability. • These results support NIVO + RELA as a first-line option for melanoma. [ABSTRACT FROM AUTHOR]

Background: Nivolumab at a dose of 480 mg every 4 weeks (Q4W) is approved for the adjuvant treatment of melanoma. However, real‐world data on this regimen are limited in this setting. Methods: This retrospective observational study utilized data from the US Oncology Network iKnowMed electronic health record database and patient medical charts. Eligible patients were diagnosed with melanoma and received adjuvant nivolumab monotherapy from March to August 2018. Patients were grouped by dosing regimen: cohort 1 (C1), de novo nivolumab 480 mg Q4W; cohort 2 (C2), switched to nivolumab 480 mg Q4W after nivolumab 240 mg or 3 mg/kg every 2 weeks (Q2W); cohort 3 (C3), de novo nivolumab 3 mg/kg Q2W; or cohort 4 (C4), de novo nivolumab 240 mg Q2W. Patients were followed for up to 12 months. Duration of therapy and safety/tolerability were assessed. Results: One hundred ninety‐one patients were included (C1, n = 40; C2, n = 74; C3, n = 22; C4, n = 55). Duration of therapy was relatively consistent across cohorts (median, 10.3 months; range, 8.3–10.7). Likewise, proportions of patients experiencing treatment‐related adverse events (TRAEs) were similar (range, 54.5%–60.1%), as were the most common events (fatigue, rash, diarrhea, hypothyroidism, nausea, and pruritus). However, proportions experiencing 'significant' TRAEs varied between cohorts. Proportions discontinuing treatment were relatively consistent across cohorts. Propensity score matching and sensitivity analyses generally supported the unadjusted findings. Conclusions: Real‐world safety profiles of nivolumab 240 mg Q2W and 480 mg Q4W were similar, and both were comparable to the well‐documented safety of weight‐based dosing (3 mg/kg Q2W), further supporting their approval and use in the adjuvant setting for melanoma. [ABSTRACT FROM AUTHOR]

Nivolumab (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. An 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. Nivolumab 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. This 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. • Nivolumab is an adjuvant treatment for patients with high-risk resected melanoma. • This indirect treatment comparison (ITC) compared adjuvant nivolumab with placebo. • Placebo was the proxy for a watch-and-wait strategy. • Data used in the ITC were from two phase III trials. • Adjuvant nivolumab improved efficacy versus placebo in high-risk resected melanoma. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the current study is to estimate the cost-effectiveness of adjuvant treatment with nivolumab relative to clinically relevant comparators in adult patients with melanoma with lymph node involvement or metastatic disease who have undergone complete resection from a French societal perspective. Methods: The comparators were observation, low-dose interferon and pembrolizumab. A subgroup analysis was carried out in patients with BRAF mutation, adding dabrafenib plus trametinib. A three-state partitioned survival model was developed to project costs and health benefits over a 20-year time horizon. Extrapolation for recurrence-free survival (RFS) and overall survival (OS) was carried out using spline-based models. Because of the immaturity of OS data in pivotal trials for nivolumab and pembrolizumab, a predictive model of OS treatment effect based on RFS effect was developed using a correlation equation. Health state utilities and adverse events disutilities were derived from the CheckMate 238 trial and literature. Costs were estimated in 2019 euros. The model's primary outcome was efficiency frontier. Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of results. Results: Observation, low-dose interferon and nivolumab were on the efficiency frontier. The incremental cost–utility ratio of nivolumab versus low-dose interferon (closest therapy on the efficiency frontier) was €37,886/quality-adjusted life year (QALY). Probabilistic sensitivity analysis reported an 80% probability of nivolumab being a cost-effective strategy for a willingness-to-pay threshold of €52,000/QALY. In the subgroup with BRAF mutation, the efficiency frontier was not changed by the addition of dabrafenib plus trametinib. Conclusions: Nivolumab is a cost-effective strategy as adjuvant treatment in adult patients with surgically resected melanoma in France. [ABSTRACT FROM AUTHOR]

Recent changes in the adjuvant treatment of melanoma have raised interest in confirming relapse-free survival (RFS) as a surrogate for overall survival (OS). We explore this issue with the meta-analytic framework, using individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 18071 trial of ipilimumab and published results from other adjuvant trials. The individual patient data analysis results at a median follow-up of 5.3 years showed a strong association between RFS and OS at the patient level (ρ = 0.84; 95% confidence interval [CI]: 0.82–0.87) and a moderate association at the trial level (R2 = 0.59; 95% CI: 0.08–1.00). The trial-level association previously observed in interferon-based trials appeared to be maintained when the EORTC 18071 results were added to a regression analysis using published results from other trials. More data from adjuvant trials are required to confirm the strength of association between RFS and OS in this setting. • We explored relapse-free survival (RFS) as a surrogate for overall survival (OS). • We used data from the European Organisation for Research and Treatment of Cancer 18071 trial and published results from other trials. • We found a strong association between RFS and OS at the patient level. • We found a moderate association between RFS and OS at the trial level. • Our results are promising and require confirmation with a larger number of trials. [ABSTRACT FROM AUTHOR]