Platinum Selection in Immune Checkpoint Inhibitor-Based Therapy for Recurrent or Metastatic Head and Neck Cancer: A Multi-Institutional Retrospective Study

The KEYNOTE-048 trial established pembrolizumab plus platinum and 5-fluorouracil (5-FU) as the standard first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). In the present study, the efficacy and safety of cisplatin and carboplatin in combination with pembrolizumab were compared using real-world data. In this retrospective study, 76 patients with R/M HNSCC treated with pembrolizumab plus 5-FU and either cisplatin (n=41) or carboplatin (n=35) were analysed. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and the incidence of grade ≥3 haematological and grade ≥2 non-haematological adverse events. The median PFS was 4.1 months with cisplatin and 7.1 months with carboplatin (p=0.58). The median OS values were 14.8 and 20.7 months, respectively (p=0.88). The ORR values were similar (34.1% vs. 34.3%, p=0.99). Grade ≥3 haematological adverse events were more frequent with cisplatin than with carboplatin (87.8% vs. 48.6%, p<0.01), as were grade ≥2 non-haematological adverse events (97.6% vs. 54.3%, p<0.01). Cisplatin showed no advantage over carboplatin regarding OS, PFS, and ORR but caused increased toxicity in ICI-based therapy for R/M HNSCC. These findings support carboplatin as the preferred platinum with pembrolizumab, balancing efficacy and safety.