ORIGINAL RESEARCH article
Front. Oncol.
Sec. Head and Neck Cancer
SEQUENTIAL SALVAGE SYSTEMIC THERAPY AFTER IMMUNOTHERAPY IN HEAD AND NECK CANCER: A REAL-WORLD STUDY
Provisionally accepted
Santiago Cabezas-Camarero1*
Salomé Merino-Menéndez1
María Nieves Cabrera-Martín1Pablo Pérez-Alonso1
Miguel Sotelo2
Pedro Pérez Segura1- 1San Carlos University Clinical Hospital, Madrid, Spain
- 2Hospital Maria Auxiliadora, San Juan de Miraflores, Peru
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Background: There is not an established standard therapy after progression to immune checkpoint inhibitors (ICI). Retrospective and limited prospective studies suggest that salvage chemotherapy after ICI (SCAI) may outperform historical pre-ICI data in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). We evaluated cetuximab-based SCAI outcomes in a real-world setting. Methods: Objective response rate (ORR), median duration of response (DoR), and median best percentage change in target lesions (PCTL) by RECIST 1.1, and median progression-free survival (PFS) and overall survival (OS) with SCAI and with last chemotherapy before immunotherapy (LCBI) were assessed. Adverse events (AEs) by CTCAE 5.0, were evaluated during SCAI, as well as treatment exposure to cetuximab-based therapy and to ICI along the whole R/M setting. Results: Among 80 patients, 96% and 100% received cetuximab-based 1st and 2nd SCAI, respectively, primarily as weekly (90%–94%) regimens. 1st-SCAI: ORR 59% (41/70; 31 partial, 10 complete responses), PCTL −57% (range, −30% to −100%), DoR 9.4 months, PFS and OS 5.9 and 12.4 months; 1st-line OS: 24 months. Cetuximab-based exposure (256 days) significantly exceeded ICI exposure (168.5 days; p=0.038). LCBI-treated (n=22): ORR 36% (LCBI) vs. 47% (SCAI), PFS 8 months (LCBI) vs. 4.4 months (SCAI); 1st-line OS 25.9 months. 2nd SCAI (n=17): ORR 30% (3/10), PFS and OS of 3.5 and 7 months; 1st-line OS 21.7 months. Grade 1–2 AEs: 100%; grade 3–5 AEs: 38.7% (1st SCAI) and 47% (2nd SCAI) with no toxic deaths. Conclusion: Cetuximab-based SCAI post-ICI showed high rates of response, which were durable and profound, and improved survival compared to historical data, with modest efficacy in re-sequenced patients. Time on cetuximab was significantly longer than on ICI. These results should be confirmed in a larger prospective study.
Keywords: cetuximab, head and neck cancer, immune checkpoint inhibitors, Rechallenge, Sequential therapy
Received: 06 Oct 2025; Accepted: 09 Dec 2025.
Copyright: © 2025 Cabezas-Camarero, Merino-Menéndez, Cabrera-Martín, Pérez-Alonso, Sotelo and Pérez Segura. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Santiago Cabezas-Camarero
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