Prognostic impact of baseline tumour immune infiltrate on disease-free survival in patients with completely resected, BRAFv600 mutation–positive melanoma receiving adjuvant vemurafenib

P. A. Ascierto, K. D. Lewis, A. M. Di Giacomo, L. Demidov, M. Mandalà, I. Bondarenko, C. Herbert, A. Mackiewicz, P. Rutkowski, A. Guminski, B. Simmons, C. Ye, G. Hooper, M. J. Wongchenko, G. R. Goodman, Y. Yan, D. Schadendorf

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Abstract

Background: We conducted a retrospective exploratory analysis to evaluate the effects of baseline tumour immune infiltrate on disease-free survival (DFS) outcomes in patients with fully resected stage IIC–IIIC melanoma receiving adjuvant vemurafenib monotherapy or placebo in the BRIM8 study. Patients and methods: BRIM8 was a phase III, international, double-blind, randomised, placebo-controlled study. Eligible patients with BRAFV600 mutation–positive, completely resected melanoma were randomly assigned to oral vemurafenib (960 mg twice daily) or matching placebo for 52 weeks. The primary end point was DFS. The association of CD8+ T-cell infiltration and programmed death ligand 1 (PD-L1) expression with DFS, as measured by immunohistochemistry, was explored retrospectively. Results: Four hundred ninety-eight patients were randomly assigned to receive adjuvant vemurafenib (n = 250) or placebo (n = 248); tumour samples were available for biomarker analysis for approximately 60% of patients. In the pooled biomarker population, placebo-treated patients with <1% CD8+ T cells in the tumour centre had shorter median DFS than those with ≥1% CD8+ T cells (7.7 versus 47.8 months). DFS benefit from vemurafenib versus placebo was greater in patients with <1% CD8+ T cells [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.34–0.92) than in patients with ≥1% CD8+ T cells (HR 0.77; 95% CI 0.48–1.22). Likewise, median DFS was shorter among placebo-treated patients with <5% versus ≥5% PD-L1+ immune cells (IC) in the tumour (7.2 versus 47.8 months). A greater DFS benefit with vemurafenib versus placebo was observed in patients with <5% PD-L1+IC (HR 0.36; 95% CI 0.24–0.56) than in patients with ≥5% PD-L1+IC (HR 0.99; 95% CI 0.58–1.69). Conclusions: The presence of CD8+ T cells and PD-L1+IC are favourable prognostic factors for DFS. Treatment with adjuvant vemurafenib may overcome the poor DFS prognosis associated with low CD8+ T-cell count or PD-L1 expression. ClinicalTrials.gov identifier: NCT01667419

Original languageEnglish
Pages (from-to)153-159
Number of pages7
JournalAnnals of Oncology
Volume31
Issue number1
DOIs
Publication statusPublished - Jan 2020

Keywords

  • adjuvant therapy
  • melanoma
  • vemurafenib

ASJC Scopus subject areas

  • Hematology
  • Oncology

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    Ascierto, P. A., Lewis, K. D., Di Giacomo, A. M., Demidov, L., Mandalà, M., Bondarenko, I., Herbert, C., Mackiewicz, A., Rutkowski, P., Guminski, A., Simmons, B., Ye, C., Hooper, G., Wongchenko, M. J., Goodman, G. R., Yan, Y., & Schadendorf, D. (2020). Prognostic impact of baseline tumour immune infiltrate on disease-free survival in patients with completely resected, BRAFv600 mutation–positive melanoma receiving adjuvant vemurafenib. Annals of Oncology, 31(1), 153-159. https://doi.org/10.1016/j.annonc.2019.10.002