Clinical outcomes in metastatic uveal melanoma treated with PD‐1 and PD‐L1 antibodies

Abstract

BACKGROUND Antibodies inhibiting the programmed death receptor 1 (PD-1) have shown significant activity in the treatment of advanced cutaneous melanoma. The efficacy and safety of PD-1 blockade in patients with uveal melanoma has not been well characterized. METHODS 58 stage IV uveal melanoma patients received PD-1 or PD-L1 antibodies between 2009 and 2015 at nine academic centers. Patients who were evaluable for response were eligible for analysis. Imaging was performed every 12-weeks and at the investigators’ discretion. Safety and clinical efficacy outcomes including best overall response (BOR), progression-free survival (PFS), overall survival (OS) were determined retrospectively. RESULTS Of 56 eligible patients, 48 (86%) had received prior therapy and 35 (63%) had been treated with ipilimumab. Three patients had an objective response to ipilimumab and 8 patients had stable disease as the best response. 38 (68%) received pembrolizumab, 16 (29%) received nivolumab, and 2 (4%) received atezolizumab. Objective tumor responses were observed in two patients for an overall response rate of 3.6% (95% CI 1.8-22.5%). Stable disease (≥ 6 months) was observed in 5 (9%) patients. The median PFS was 2.6 months (95% CI 2.4-2.8 months) and the median OS was 7.6 months (95% CI 0.7-14.6 months). There was no association between prior treatment with ipilimumab or liver directed therapy and PFS or OS. Treatment was well tolerated and only 1 patient discontinued treatment due to toxicity. CONCLUSIONS PD-1 and PD-L1 antibodies rarely confer durable remissions in patients with metastatic uveal melanoma. Clinical trial enrollment should be prioritized in this population.

Anti-PD1 treatment in metastatic uveal melanoma in the Netherlands

“…Moreover, the number and location of metastases was not described by Kottschade et al In another recent study from Algazi et al, a total of 56 patients were treated with a PD-1 or PD-L1 antibody. The median PFS was 2.6 months and the median OS was 7.6 months, which is comparable to the median PFS in our study of 2.3 months and the median OS of 9.6 months [14]. Algazi et al concluded that PD-1 and PD-L1 antibodies rarely confer durable remissions in patients with metastatic UM.…”

PD-L1 Expression in Tumor Metastasis is Different Between Uveal Melanoma and Cutaneous Melanoma

“…MUM patients are often treated with immune checkpoint inhibitors identical to those used in the treatment of MCM (anti-programmed death-1 [PD-1] and anti-CTLA4 [Cytotoxic T-lymphocyte-associated protein 4] antibodies), either as monotherapy or in combination. Contrary to MCM, MUM demonstrates a poor response to these immune checkpoint blockades [15] (Table 1) [16][17][18][19][20][21][22][23] One of the mechanisms by which tumors evade the immune system is through upregulation and expression of PD-L1 protein on their surface. PD-L1 on tumor cells interacts with PD-1 receptor expressed on activated T cells, leading to T-cell exhaustion, anergy and ultimately, immune response abandonment [24,25].…”

Ipilimumab Activity in Advanced Uveal Melanoma: A Pooled Analysis

“…More recently, there have been studies with anti-programmed cell death protein 1 antibody (anti-PD1) monotherapy and targeted therapy with MEK inhibitors that have demonstrated some activity [23][24][25]. Although at least one small series has observed activity with pembrolizumab, more extensive experience suggests that responses and clinical benefit are much more limited than with advanced cutaneous melanoma [23,24].…”

“…Although at least one small series has observed activity with pembrolizumab, more extensive experience suggests that responses and clinical benefit are much more limited than with advanced cutaneous melanoma [23,24]. The role of the newer agents in the treatment landscape for advanced UM needs to be determined and clinically justified bearing in mind the toxicity seen especially with targeted therapy [25].…”