Efficacy of anti-PD-1 therapy in patients with melanoma brain metastases

Sagun Parakh, John J. Park, Shehara Mendis, Rajat Rai, Wen Xu, Serigne Lo, Martin Drummond, Catherine Rowe, Annie Wong, Grant McArthur, Andrew Haydon, Miles C. Andrews, Jonathan Cebon, Alex Guminski, Richard F. Kefford, Georgina V. Long, Alexander M. Menzies, Oliver Klein, Matteo S. Carlino*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Citations (Scopus)

Abstract

Background:There is limited data on the efficacy of anti-programmed death 1 (PD-1) antibodies in patients (pts) with melanoma brain metastasis (BM), particularly those which are symptomatic.Method:We retrospectively assessed pts with melanoma BM treated with PD-1 antibodies, nivolumab and pembrolizumab. Clinicopathologic and treatment parameters were collected and outcomes determined for intracranial (IC) response rate (RR) using a modified RECIST criteria, with up to five IC target lesions used to determine IC response, disease control rate (DCR) and progression-free survival (PFS).Results:A total of 66 pts were identified with a median follow up of 7.0 months (range 0.8-24.5 months). A total of 68% were male and 45% BRAF V600 mutation positive. At PD-1 antibody commencement, 50% had an elevated LDH; 64% had local therapy to BM prior to commencing anti-PD1, of which 5% had surgical resection, 14% stereotactic radiosurgery (SRS), 18% whole-brain radiotherapy (WBRT), 27% had surgery and radiotherapy. Twenty-one per cent started anti-PD-1 as first line systemic therapy. No pt had prior anti-PD-1 treatment. The IC overall RR was 21 and DCR 56%. Responses occurred in 21% of pts with symptomatic BM. The median OS was 9.9 months (95% CI 6.93-17.74). Pts with symptomatic BM had shorter PFS than those without symptoms (2.7 vs 7.4 months, P=0.035) and numerically shorter OS (5.7 vs 13.0 months, P=0.068). Pts requiring corticosteroids also had a numerically shorter PFS (3.2 vs 7.4 months, P=0.081) and OS (4.8 vs 13.1 months, P=0.039).Conclusions:IC responses to anti-PD-1 antibodies occur in pts with BM, including those with symptomatic BM requiring corticosteroids. Prospective trials evaluating anti-PD-1 therapy in pts with BM are underway.

Original languageEnglish
Pages (from-to)1558-1563
Number of pages6
JournalBritish Journal of Cancer
Volume116
Issue number12
DOIs
Publication statusPublished - 6 Jun 2017

Keywords

  • anti-PD1 therapy
  • brain metastases
  • corticosteroids
  • metastatic melanoma
  • nivolumab
  • pembrolizumab

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