Real-world treatment sequences and outcomes in recurrent/metastatic head and neck squamous cell carcinoma in France (TERENCE study)

Background Recurrent and/or metastatic head and neck squamous cell carcinoma (R/M SCCHN) is aggressive, with limited therapeutic options. Guidelines recommend immunotherapy (IO) or cetuximab ± chemotherapy 1 st -line, depending on patient/tumour characteristics. Data on subsequent treatment sequencing are limited. We investigated treatment sequences for R/M SCCHN in France. Methods Patients with R/M SCCHN who received 1 st -line pembrolizumab or cetuximab (November 2020–December 2022) were identified retrospectively from a hospital discharge database, which covers 85% of the French population. Treatment sequences, overall survival (OS) and time to next treatment or death (TTNT-D) were analysed. Outcomes were compared between sequences of interest (pembrolizumab-based 1 st -line followed by cetuximab ± chemotherapy, or vice versa). Results Of 4757 patients who received 1 st -line IO or cetuximab, 2529 (53%) received 2 nd -line. Fewer patients who received IO-based vs. cetuximab-based 1 st -line treatment received 2 nd -line (45.4% vs. 61.5%): more on 1 st -line IO reached end of follow-up without 2 nd -line (26.6% vs. 8.2%). 2 nd -line/subsequent treatments were heterogeneous. For patients receiving ≥1 treatment line, median OS was 13.2 months overall (15.4 months for patients receiving ≥2 lines). For 1,742 patients who received sequences of interest, there were no significant differences between 1 st -line IO vs. cetuximab for OS (hazard ratio [HR] 0.98, [95%CI 0.90, 1.11], p=0.84) or TTNT-D (HR 0.92 [0.83, 1.03]. p=0.15). Conclusions In this nationwide cohort study, OS did not differ significantly between patients who received IO followed by cetuximab vs. cetuximab followed by IO. These findings support flexibility in treatment sequencing and highlight the need for further research to optimize treatment strategies.