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

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.

Figure 1

Radiological examples of intracranial response. Intracranial responses seen with anti-PD-1 therapy. (A) MRI showing a partial response in a patient with symptomatic brain metastases on 4 mg dexamethasone at baseline and 6 months later. (B) MRI showing a partial response seen in a patient on anti-PD-1 therapy with no prior local intracranial therapy at baseline and 2 months later.

Figure 2

Swimmer’s plot showing durable responses in patients who achieved an objective response to anti-PD1 therapy.

Figure 3

Intracranial PFS and OS. (A) The overall median intracranial PFS was 5.3 months (95% CI 3.3–8.2 months). (B) The median OS was 9.9 months (95% CI 6.9–17.7).

Figure 4

Impact of CNS symptoms and steroids on intracranial PFS and OS. (A) The intracranial progression-free survival (PFS) was significantly lower in patients with symptomatic brain metastases than in asymptomatic patients: 2.7 vs 7.4 months (HR 1.95 (95% CI 1.05–3.63), P=0.0348). (B) Patients with symptomatic brain metastases had a shorter median survival than patients with asymptomatic metastases: 5.7 vs 13.0 months (HR 1.91 (95% CI 0.95–3.84), P=0.068). (C) Patients on corticosteroids had a shorter PFS than those not on corticosteroids: 3.2 vs 7.4 months (HR 1.72 (95% CI 0.93–3.17), P=0.081). (D) Patients on corticosteroids had a shorter OS than those not on corticosteroids: 4.8 vs 13.1 months (HR 2.06 (95% CI 1.04–4.11) P=0.039).