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

Date

10 Oct 2016

Session

Melanoma and other skin tumours

Presenters

John Park

Citation

Annals of Oncology (2016) 27 (6): 379-400. 10.1093/annonc/mdw379

Authors

J.J. Park1, S. Parakh2, S. Mendis3, R. Rai4, S. Lo4, A. Haydon3, M.C. Andrews2, J. Cebon2, A. Guminski4, R. Kefford1, G.V. Long4, A.M. Menzies4, O. Klein2, M.S. Carlino1

Author affiliations

  • 1 Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, 2145 - Sydney/AU
  • 2 Department Of Medical Oncology, Olivia Newton-John Cancer and Wellness Centre, Austin Hospital, 3084 - Melbourne/AU
  • 3 Medical Oncology, Alfred Hospital, Melbourne/AU
  • 4 Melanoma, Melanoma Institute of Australia and The University of Sydney, 2006 - Sydney/AU
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Background

Patients (pts) with metastatic melanoma and untreated, symptomatic or progressing brain metastasis (BM) have a poor prognosis and have been excluded from the published trials of the anti-programmed death 1 (PD-1) antibodies pembrolizumab and nivolumab; as a result there is limited data on the efficacy and safety of these agents in this cohort of patients.

Methods

We retrospectively assessed the efficacy of PD-1 agents in pts with metastatic melanoma with BM treated across four centres. Patient demographics, tumour characteristics, and treatment history including corticosteroid use were collected. Intracranial (IC) and extracranial (EC) response rates (RR) and progression-free survival (PFS) were analysed. Response was determined by modified RECIST where up to 5 IC target lesions were used for IC assessment.

Results

81 pts were identified with interim analysis of 39 reported here with median F/U of 8.5 months (95% CI 5.1 to 11.4). 77% pts were male. At PD-1 inhibitor commencement, 56% had an elevated LDH; 64%, 26% and 10% had an ECOG of 0-1, 2 and >2 respectively. Median no. of IC lesions was 4 (range 1-20). 26 (67%) had local therapy (RT or surgery) to BM prior to PD-1 therapy. 23 (59%) were BRAF mutant, 9 (23%) started anti-PD-1 as 1st line therapy. Dexamethasone was used in 13 (33%) pts with dose range of 0.5 – 8mg. The IC RR was 10/39 (26%), including pts with symptomatic BM and pts receiving steroids (see Table). 2/10 IC RR had no prior RT (SRS or WBRT), 3/10 had concurrent RT and 5/10 had prior RT. The EC RR was 6/35 (17%).

Best IC response All pts (N = 39) Symptomatic BM (N = 18) Corticosteroids for BM (N = 13) Radiotherapy prior to or during PD-1 (N = 28)
CR/PR 10 2 2 8
SD 8 5 4 8
PD 12 5 5 8
Clinical PD (without imaging) 9 6 2 4
Median IC PFS was 2.1 months (95% CI 1.3 – 2.9) and median EC PFS was 2.1 months (95% CI 1.9 – 3.4). Updated analysis with the full cohort and with longer follow-up will be presented.

Conclusions

IC responses to anti-PD-1 agents were seen in pts with symptomatic BM and those requiring corticosteroids. Prospective trials evaluating anti-PD-1 therapy in pts with BM are underway, although pts with the poor prognostic features included in this series are unlikely to be represented in prospective trials.

Clinical trial identification

Legal entity responsible for the study

Melanoma Institute Australia, Medical Oncology Department, Westmead Hospital

Funding

Melanoma Institute Australia, Medical Oncology Department, Westmead Hospital

Disclosure

R. Kefford: Advisory boards: Merck, BMS. Honoraria: Merck, BMS Conference Reporting: BMS. G.V. Long: Consultant Advisor to Amgen, BMS, Merck, Novartis and Roche. Honoraria Merck, Novartis and BMS. A.M. Menzies: Advisory board - MSD, Chugai; Honoraria - BMS, Novartis. M.S. Carlino: Advisory board member for MSD, BMS, Amgen, Novartis. Honoraria: MSD, BMS, Novartis. All other authors have declared no conflicts of interest.

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