Progression and mortality post-immunotherapy discontinuation among patients with BRAFV600-mutant (BRAF+) metastatic melanoma.

Abstract

9531 Background: Immunotherapy (IO) is commonly used to treat BRAF+ metastatic melanoma (MM) patients in the first line (1L) setting and has demonstrated durable outcomes in clinical trials. However, most patients discontinue IO therapy for toxicity, disease progression, or other reasons. To date, no multi-center or nationwide US-based study has examined treatment patterns and outcomes for patients with BRAF+ MM post discontinuation of 1L IO. The aim of this study is to describe real-world treatment patterns and outcomes among patients who discontinued 1L IO. Methods: This retrospective cohort study used the Novartis BRAF+ meLanoma patients ObsErvational (NOBLE) database, the harmonized customized data from Flatiron and ConcertAI. Patients were ≥18 years old, had a diagnosis of BRAF+ MM, were treated with pembrolizumab, nivolumab, or ipilimumab + nivolumab on or after 9/1/2014, and then discontinued 1L therapy. Reason for discontinuation was extracted from medical records. Descriptive statistics were used to describe baseline characteristics and treatment patterns. Kaplan–Meier curves were used to analyze time to progression or death (TTPD) and time to death (TTD). Results: Of the 898 included patients (mean age: 61 years; male: 65%); 46% initiated ipilimumab + nivolumab, 24% nivolumab, and 30% pembrolizumab. The most common reasons for 1L discontinuation were toxicity (26%) and progression (25%). Medical records noted 5.3% completed therapy on discontinuation and 34.5% provided no reason of discontinuation with median duration of therapy (MDOT) of 379 and 138 days respectively. At 6 months, 34 % (n = 303) remain on IL IO. MDOT for patients who discontinued IO due to toxicity and those who discontinued due to progression were 54 and 63.5 days respectively. Patients who discontinued due to toxicity had a median time of 142 days to next treatment. TTPD was best for patients who discontinued therapy due to completion or toxicity (6-month progression rate: 13% and 20%). Patients who discontinued due to progression did especially poorly (6-month progression rate: 59%). About 33% of patients (n = 296) needed second line (2L) therapy, and the majority (80.7%) received combination BRAF+ targeted therapy. Overall, 38% and 50% of patients died post IO discontinuation for any reason at 1 and 2 years, respectively. 31% of patients had brain metastases and a greater proportion (56%) died within a 2-year period compared with those without brain metastases (56% vs 49%, p = 0.0036). Conclusions: IO, although effective, is not curative for all patients. A significant number of patients discontinue therapy due to progression. Patients with BRAF+ MM who progress early on 1L IO therapy have a high risk of death and should be considered for other therapy options, including targeted therapy.