PD-1 blockade synergizes with oxaliplatin-based, but not cisplatin-based, chemotherapy of gastric cancer.

Preclinical experimentation revealed that established cancers treated with the immunogenic cell death (ICD) inducer oxaliplatin are sensitized to immune checkpoint inhibitors targeting PD-1. In contrast, no such sensitizing effect is observed when cisplatin, a non-immunogenic cell death inducer is used. Two randomized phase III clinical trials targeting unresectable gastric and gastro-esophageal junction carcinomas apparently validate this observation. Thus, oxaliplatin-based chemotherapy (together with capecitabine or 5-fluorouracil plus leucovorin) favorably interacted with nivolumab, yielding improved outcome. In contrast, the outcome of cisplatin-based chemotherapy (together with capecitabine or 5-fluorouracil) failed to be improved by concomitant treatment with pembrolizumab. These clinical findings underscore the importance of choosing appropriate ICD-inducing cytotoxicants for the development of chemoimmunotherapeutic regimens. Unfortunately, the FDA and EMA have approved PD-1 blockade in combination with "platinum-based chemotherapy" without specifying the precise nature of the platinum-containing drug. This is a non sequitur. Based on the available clinical data, such approvals should be restricted to the use of oxaliplatin.

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© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

Déclaration de conflit d'intérêts

GK and OK are cofounders of Samsara Therapeutics. GK is a cofounder of Therafast Bio. AH participates on data safety monitoring or consulting and advisory boards for Amgen, BMS, Basilea, Incyte, Servier, QED Therapeutics, Tahio, and Relay Therapeutics.