Targeted Agents or Immuno-Oncology Therapies as First-Line Therapy for BRAF-Mutated Metastatic Melanoma: A Real-World Study

Abstract

Aim: Targeted therapy (TT) and immuno-oncology (IO) drugs are approved for patients with BRAF mutant metastatic melanoma (MM). We compared real-world outcomes for first-line (1L) TT versus 1L IO to evaluate optimal sequencing. Materials & methods: Physicians-identified BRAF mutant MM patients initiating 1L TT or IO therapies and extracted treatment, disease and clinical outcomes including disease response which were compared between TT and IO and individual regimens. Results: 440 MM patients (TT = 283, IO = 157) were identified. A higher proportion of TT patients had liver metastases (46.3 vs 35.0%) and abnormal lactate dehydrogenase (61.1 vs 42.7%). IO-treated had a RECIST-determined response rate of 45.9 versus 60.1% for TT and time on treatment of 7.2 versus 11.4 months, respectively. There was no survival difference between cohorts. Conclusion: Despite higher risk patients, 1L TT resulted in higher response rate and longer treatment duration suggesting a preferred 1L sequence.

An observational study of drug utilization and associated outcomes among adult patients diagnosed with BRAF‐mutant advanced melanoma treated with first‐line anti‐PD‐1 monotherapies or BRAF/MEK inhibitors in a community‐based oncology setting

“…The proportions of patients advancing from 1L to 2L and 3L are consistent with similar studies of community‐based care of melanoma. In the real‐world study of patients with BRAF‐mutant advanced melanoma initiating 1L treatment, Luke et al (2019) reported that only 49.8% received 1L treatment, 43.5% received both 1L and 2L, and only 6.7% received 3L 29 . In another real‐world study of treatment‐naïve patients with BRAF‐mutant advanced melanoma, Whitman et al (2019) found that 57.0% of the BRAF‐mutant cohort received only 1L, 28.0% 1L and 2L, and 15.0% 3L+ 26 .…”

Author’s Response to “A Letter in Support of Real-World RECIST”

“…We appreciate the opportunity to discuss and clarify our findings [1]. Although the letter authors' work complements our own [2][3][4][5], the objectives and the methods differ. For example, in Feinberg et al, Response Evaluation Criteria in Solid Tumors (RECIST) was applied to realworld imaging data that were submitted in case report forms by compensated physicians.…”

Distinct Genomic Features Across Cytolytic Subgroups in Skin Melanoma

“…With the advent of immunotherapies, the tumor's management has shifted from cytokine-based treatment to immune checkpoint inhibition, primarily of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell-death protein 1 (PD-1) or its ligands (PD-L1 and PD-L2) [15][16][17][18]. Monoclonal antibodies including Ipilimumab, Tremelimumab (anti-CTLA-4), Pembrolizumab, Nivolumab, Cemiplimab (anti-PD-1), Atezolizumab, Avelumab and Durvalumab (anti-PD-L1), among others currently being on clinical trial [19], have enthusiastically provided longlasting responses and improved survival in patients with advanced-stage metastatic melanoma [16].…”