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Comparative Study
. 2016 Nov 15;122(21):3344-3353.
doi: 10.1002/cncr.30258. Epub 2016 Aug 17.

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

Alain P Algazi  1 , Katy K Tsai  2 , Alexander N Shoushtari  3 , Rodrigo R Munhoz  3 , Zeynep Eroglu  4 , Josep M Piulats  5 , Patrick A Ott  6 , Douglas B Johnson  7 , Jimmy Hwang  2 , Adil I Daud  2 , Jeffrey A Sosman  7 , Richard D Carvajal  8 , Bartosz Chmielowski  9 , Michael A Postow  3 , Jeffrey S Weber  10 , Ryan J Sullivan  11
Affiliations
Comparative Study

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

Alain P Algazi et al. Cancer. .

Abstract

Background: Antibodies inhibiting the programmed death receptor 1 (PD-1) have demonstrated 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: Fifty-eight patients with stage IV uveal melanoma received PD-1 or PD-1 ligand (PD-L1) antibodies between 2009 and 2015 at 9 academic centers. Patients who were evaluable for response were eligible for the analysis. Imaging was performed every 12 weeks and at the investigators' discretion. Safety and clinical efficacy outcomes, including the best overall response, progression-free survival (PFS), and overall survival (OS), were retrospectively determined.

Results: Of 56 eligible patients, 48 (86%) had received prior therapy, and 35 (63%) had received treatment with ipilimumab. Three patients had an objective response to ipilimumab, and 8 had stable disease as their best response. Thirty-eight patients (68%) received pembrolizumab, 16 (29%) received nivolumab, and 2 (4%) received atezolizumab. Objective tumor responses were observed in 2 patients for an overall response rate of 3.6% (95% confidence interval [CI], 1.8%-22.5%). Stable disease (≥6 months) was observed in 5 patients (9%). 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 because of 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. Cancer 2016;122:3344-3353. © 2016 American Cancer Society.

Keywords: atezolizumab; immunotherapy; nivolumab; pembrolizumab; uveal melanoma.

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Conflict of interest statement

Conflict of Interest: Alain Algazi serves as Principal Investigator at UCSF for studies supported by Merck and Bristol-Myers-Squibb. Katy Tsai reports no relevant disclosures. Douglas Johnson serves on advisory boards for Bristol-Myers-Squibb and Genoptix. Alexander Shoushtari serves as PI at MSKCC for studies supported by BMS and has served on the scientific advisory board for Vaccinex. Richard Carvajal serves on advisory boards for Merck and Genentech.

Figures

Figure 1
Figure 1. Best overall responses
Best overall response data assessed as the greatest percent change in tumor diameters available for 48 patients. 8 patients who died within 16 weeks without available follow-up images are not included. 39 patients had a net increase in the sum of tumor diameters or progression of non-target lesions as the best response (Panel A). Serial imaging of a liver mass in a 61 year-old man with metastatic uveal melanoma responding to pembrolizumab (Panel B).
Figure 2
Figure 2. PFS and OS estimates
Kaplan-Meier curves showing progression free survival (Panel A) and overall survival (Panel B) in all 56 patients.
See this image and copyright information in PMC

Comment in

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