Background and aim: We aimed from the current study to explore the treatment results of cetuximab in combination with a weekly carboplatin and paclitaxel regimen in advanced squamous cell carcinoma of head and neck (HNSCC) after failure of radiotherapy and chemotherapy.

Methods: This study was a non-randomised, single arm, phase 2 efficacy study conducted in two oncology centres in upper Egypt, we recruited 31 patients with recurrent HNSCC previously treated with concurrent chemoradiation ± surgery to receive weekly cetuximab, carboplatin and paclitaxel for 18 weeks followed by maintenance cetuximab every 2 weeks for 12 months. All patients underwent intention to treat analysis.

Results: The current study revealed a significant reduction of the size of recurrent primary lesion (p < 0.001), without comparable significant reduction of regional lymph nodes (LNs) (p = 0.06), the current overall response rate (ORR) was 83.9%, ≥1-year progression-free survival (PFS) was 58.1%, also surgical intervention was succeeded to salvage 32.3% who did not achieve complete response to the current protocol, the median PFS was 12 months which was significantly affected by tumour site (p = 0.012), programmed death ligand-1 (PDL-1) expression (p = 0.01) and overall response rate (ORR) (p < 0.001).

Conclusion: Based on favourable treatment outcomes, including high ORR and disease control rate, improved median PFS and tolerable toxicity profile, the current weekly cetuximab, carboplatin and paclitaxel with 1 year maintenance cetuximab in responding patients is considered a feasible and effective regimen.