Prognostic Model for Treatment Outcomes in BRAF V600–Mutated Metastatic Melanoma

Key Points

  • Among all patients, baseline factors associated with progression-free survival were LDH, ECOG performance status, presence or absence of liver metastases, and SLD.
  • Among all patients, baseline factors associated with overall survival were LDH, ECOG performance status, and SLD.

In a study reported in JAMA Oncology, Hauschild et al identified baseline lactate dehydrogenase (LDH), performance status, disease burden, and gene signature as potential determinants of treatment outcomes in BRAF V600–mutant metastatic melanoma treated with BRAF and/or MEK inhibitors.

Study Details

The study was a retrospective and exploratory recursive partitioning analysis (RPA) modeling associations between prespecified baseline prognostic factors and survival outcomes regardless of treatment using pooled data from the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies.

The RPA included 1,365 patients (57% male; 76% aged > 65 years); of these, 310 received cobimetinib (Cotellic) plus vemurafenib (Zelboraf), 717 vemurafenib alone, and 338 dacarbazine.

Treatment Outcomes by Baseline Factors

Median follow-up was 14.1 months. In the RPA including all patients, baseline LDH, Eastern Cooperative Oncology Group (ECOG) performance status, presence or absence of liver metastases, and baseline sum of longest diameters of target lesions (SLDs) were significantly prognostic for progression-free survival. Median progression-free survival was longest (11.1 months) in patients with lower LDH (≤ 2 times upper limit of normal), ECOG performance status of 0, and shorter SLD (≤ 44 mm); it was shortest (3.5 months) in those with elevated LDH.

Among patients in the most favorable subgroup (lower LDH, performance status of 0, and shorter SLD), 3-year progression-free survival was 51.8% in the cobimetinib/vemurafenib cohort, 26.0% in the vemurafenib-alone cohort, and 0.0% in the dacarbazine cohort.

Baseline LDH, performance status, and SLD were significant prognostic factors for overall survival; median survival was longest (27.2 months) in patients with lower LDH and shorter SLD and shortest (6.0 months) in those with elevated LDH (> 2 times upper limit of normal). Among patients in the most favorable subgroup (lower LDH and shorter SLD), 3-year overall survival was 53.3% in the cobimetinib/vemurafenib cohort, 35.6% in the vemurafenib-alone cohort, and 35.6% in the dacarbazine cohort.

Among patients with available gene expression data, gene signature was a significant prognostic factor for progression-free survival among those with lower LDH, with 3-year progression-free survival of 21.9% among those with immune signatures and 8.8% among those with cell cycle signatures. Gene signature was not a significant factor in overall survival.

The investigators concluded: “Baseline LDH, ECOG [performance status], disease burden, and gene signature appear to be key determinants of survival outcomes in patients with BRAF V600–mutated metastatic melanoma treated with BRAF and/or MEK inhibitors. These results are consistent with survival benefits of cobimetinib plus vemurafenib over vemurafenib alone observed in the coBRIM study.”

The study was funded by F. Hoffmann-La Roche Ltd.

Axel Hauschild, MD, of the Department of Dermatology, University of Kiel, is the corresponding author for the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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