Pembrolizumab and all-trans retinoic acid combination treatment of advanced melanoma: long-term survival update

Jessica S W Borgers; Theresa M Medina; William A Robinson; Kasey L Couts; Elizabeth N Katsnelson; Claire M Muckle; Eduardo Davilla; Sapna P Patel; Dexiang Gao; Richard P Tobin; Martin D McCarter

doi:10.1177/17588359251349321

Pembrolizumab and all-trans retinoic acid combination treatment of advanced melanoma: long-term survival update

Ther Adv Med Oncol. 2025 Jun 25:17:17588359251349321. doi: 10.1177/17588359251349321. eCollection 2025.

Authors

Affiliations

¹ Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
² Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
³ University of Colorado Comprehensive Cancer Center, University of Colorado School of Medicine, Aurora, CO, USA.
⁴ Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁵ Department of Pediatrics, School of Medicine, University of Colorado Cancer Center Biostatistics Core, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
⁶ Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, 12631 East 17th Avenue, C325, Aurora, CO 80045, USA.

Abstract

Background: Primary analysis of the phase I/II clinical trial combining pembrolizumab with all-trans retinoic acid (ATRA) for patients with metastatic melanoma showed a median progression-free survival (PFS) of 20.3 months and median overall survival (OS) not reached.

Objective: Report 5-year OS and PFS rates.

Design: In this single-center, single-arm trial (NCT03200847), 24 anti-PD-1 naïve patients with metastatic melanoma were enrolled between 10/2017 and 07/2020.

Methods: The Kaplan-Meier method was used to estimate OS and PFS.

Results: At data cutoff (May 14, 2024), all patients had completed treatment, and 58% (n = 14) remained alive with a median follow-up of 48 months. The updated 5-year OS rate is 54.7% (95% confidence interval (CI): 36.4-82.1), and the 5-year PFS is 36.1% (95% CI: 21.0-62.2), with 33% (n = 8) having an ongoing complete response.

Conclusion: These results underscore the long-term clinical benefit of combining anti-PD-1 with ATRA, with survival rates comparable to anti-PD-1/combinations but with lower toxicity.

Keywords: ATRA; anti-PD-1; clinical trial; immune-checkpoint blockade; melanoma.