The chemo-free approach for PDL1-positive platinum-sensitive recurrent/metastatic head and neck squamous cell carcinoma: Viable option or misguided myth?

Background: Pembrolizumab, alone (monopembro) or with chemotherapy (CT+pembro), is state-of-the-art for recurrent/metastatic head and neck cancers (RM HNSCC). Direct comparisons of progression-free (PFS) and overall survival (OS) lack, but the two options are perceived as equivalent. So, the choice of first-line therapy relies on individual judgment without solid evidence. Inferring patient survivals from published curves may provide data to make inferences. Methods: Kaplan-Meier curves from Keynote 048 trial publications were digitized and reconstructed to infer individual patient data for CPS≥ 1, CPS1–19, and CPS≥ 20 subgroups. Restricted mean survival time differences (RMSTD) in PFS and OS at 12 months were estimated to quantify survival benefits. Results: The 12-month RMSTD in PFS was significantly longer in CT+pembro over monopembro: CPS≥ 1 (1.04 months, p = 0.004), CPS1–19 (1.09 months, p = 0.027), and CPS≥ 20 (1.17 months, p = 0.027). No OS differences were observed. Discussion: The PFS benefits challenge the perception of equivalence between monopembro and CT + pembro in RM HNSCC. These results emphasize the need to reconsider chemo-free approaches in everyday practice and in clinical trial design. The implications of a PFS benefit, including quality of life, in absence of OS gain should be weighed against toxicities in shared decision-making.