Outcomes in Melanoma Patients Treated with BRAF/MEK-Directed Therapy or Immune Checkpoint Inhibition Stratified by Clinical Trial versus Standard of Care

Chloe Goldman, Jeremy Tchack, Eric M. Robinson, Sung Won Han, Una Moran, David Polsky, Russell S. Berman, Richard L. Shapiro, Patrick A. Ott, Iman Osman, Hua Zhong, Anna C. Pavlick, Melissa Ann Wilson

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Objectives: Since 2011, metastatic melanoma treatment has evolved with commercial approval of BRAF- and MEK-targeted therapy and CTLA-4- and PD-1-blocking antibodies (immune checkpoint inhibitors, ICI). While novel therapies have demonstrated improved prognosis in clinical trials, few studies have examined the evolution of prognosis and toxicity of these drugs among an unselected population. We assess whether survival and toxicity reported in trials, which typically exclude most patients with brain metastases and poor performance status, are recapitulated within a commercial access population. Methods: 182 patients diagnosed with stage IV melanoma from July 2006 to December 2013 and treated with BRAF- and/or MEK-targeted therapy or ICI were prospectively studied. Outcomes and clinicopathologic differences between trial and commercial cohorts were assessed. Results: Patients receiving commercial therapy (vs. on trial) had poorer prognostic features (i.e., brain metastases) and lower median overall survival (mOS) when assessed across all treatments (9.2 vs. 17.5 months, p = 0.0027). While toxicity within trial and commercial cohorts did not differ, patients who experienced toxicity had increased mOS (p < 0.001), irrespective of stratification by trial status or therapy. Conclusion: Metastatic melanoma patients receiving commercial treatment may represent a different clinical population with poor prognostic features compared to trial patients. Toxicity may prognosticate treatment benefit.

Original languageEnglish
Pages (from-to)164-176
Number of pages13
JournalOncology (Switzerland)
Volume93
Issue number3
DOIs
Publication statusPublished - 2017 Aug 1
Externally publishedYes

Keywords

  • Adverse events
  • Immune-related adverse events
  • Immunotherapy
  • Metastatic melanoma
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Goldman, C., Tchack, J., Robinson, E. M., Han, S. W., Moran, U., Polsky, D., Berman, R. S., Shapiro, R. L., Ott, P. A., Osman, I., Zhong, H., Pavlick, A. C., & Wilson, M. A. (2017). Outcomes in Melanoma Patients Treated with BRAF/MEK-Directed Therapy or Immune Checkpoint Inhibition Stratified by Clinical Trial versus Standard of Care. Oncology (Switzerland), 93(3), 164-176. https://doi.org/10.1159/000475715