1. Indirect treatment comparison of nivolumab versus placebo for the adjuvant treatment of melanoma.
- Author
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Hemstock, Matthew, Amadi, Adenike, Kupas, Katrin, Roskell, Neil, Kotapati, Srividya, Gooden, Kyna, Middleton, Mark R., and Schadendorf, Dirk
- Subjects
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MELANOMA prognosis , *DRUG side effects , *CANCER relapse , *COMBINED modality therapy , *COMPARATIVE studies , *CONFIDENCE intervals , *MELANOMA , *METASTASIS , *PUBLIC health surveillance , *QUALITY of life , *RISK assessment , *TUMOR classification , *TERMINATION of treatment , *EFFECT sizes (Statistics) , *TREATMENT effectiveness , *ODDS ratio - Abstract
Until recently, adjuvant treatment options for stage III and IV resectable melanoma have been limited. Patients were often managed through routine surveillance. The phase III randomised controlled trial (RCT) CheckMate 238 (238) demonstrated the safety and efficacy of nivolumab as an adjuvant treatment for melanoma in patients with stage IIIB/C or IV disease (American Joint Committee on Cancer [AJCC], 7th edition) versus ipilimumab. The study objective was to estimate the relative efficacy, safety and health-related quality of life (HRQoL) between nivolumab and routine surveillance. Indirect treatment comparisons (ITCs) of nivolumab versus placebo were constructed using data from 238 and EORTC 18071. EORTC 18071 is a phase III RCT comparing ipilimumab with placebo in patients with resected stage IIIA–IIIC melanoma (AJCC, 6th edition). ITCs were performed using the Bucher comparison method and patient-level data for efficacy, safety and HRQoL. For the efficacy outcomes, nivolumab performed significantly better than placebo for recurrence-free survival (hazard ratio [HR]: 0.53 [95% confidence interval {CI}: 0.41, 0.68]) and distant metastases-free survival (HR: 0.59 [95% CI: 0.44, 0.78]). Safety ITCs indicated that patients receiving nivolumab had a greater hazard of experiencing an adverse event (AE) and AEs leading to treatment discontinuation, whereas there was a non-significant increased hazard of experiencing a serious AE. HRQoL ITCs showed comparable time to deterioration in 14 of the 15 QLQ-C30 domains; only the dyspnoea domain significantly favoured placebo. Nivolumab was associated with significantly improved efficacy outcomes versus placebo, whereas maintaining patient's overall HRQoL. Across the different analysis and populations, there was a high level of consistency in the effect size. • The aim was to estimate the relative treatment effect between nivolumab and placebo. • ITCs in adjuvant melanoma were constructed using CheckMate238 and EORTC-18071. • ITCs showed a significant advantage of nivolumab over placebo for efficacy outcomes. • ITCs showed patient's overall HRQoL were not compromised between treatments. • Nivolumab is an important addition to the treatment options for this disease. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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