Induction chemotherapy followed by cisplatin or cetuximab concomitant to radiotherapy for laryngeal/hypopharyngeal cancer: Long-term results of the TREMPLIN randomised GORTEC trial

Background: In Europe, induction chemotherapy (ICT) followed by radiotherapy is preferred to conventional chemoradiotherapy to avoid total laryngectomy in patients with laryngeal/hypopharyngeal cancer. In comparison with conventional radiotherapy, bioradiotherapy with cetuximab significantly improves locoregional control rates (LCRs) and overall survival (OS) without any increase in unmanageable toxicity. Methods: Patients included had untreated non-metastatic stage III-IV laryngeal/hypopharyngeal invasive squamous cell carcinoma. Good responders after three cycles of docetaxel-cisplatin-5-fluorouracil (TPF)-ICT (docetaxel and cisplatin, 75 mg/m(2) each on day 1, and 5-fluorouracil, 750 mg/m(-2)/day on days 1-5) every 3 weeks were randomised to receive radiotherapy (70 Gy) with concurrent cisplatin (100 mg/m(2)/day on days 1, 22 and 43 of radiotherapy) or cetuximab (400 mg/m(2) of loading dose, 250 mg/m(2)/week during radiotherapy). The primary end-point was larynx preservation. The secondary end-points were laryngo-oesophageal dysfunction-free survival (LEDFS), LCR and OS. Results A total of 153 patients were enrolled. Among 126 TPF-ICT responders, 116 were randomised to receive either cisplatin (n = 60) or cetuximab (n = 56). The median follow-up was 77.5 months. Five-year OS rates were 66.6% (95% confidence interval [CI]: 0.54-0.79) versus 66.9% (95% CI: 0.54-0.79) (p = 0.9), respectively. Five-year LCRs were 79.8% (95% CI: 69.5-90.0) versus 67.8% (95% CI: 55.1-80.5%) (p = 0.18). Five-year LEDFS was 62.2% (95% CI: 49.7-74.8%) versus 56.2% (95% CI: 43.0-69.4) (p = 0.38). Late grade III/IV salivary gland and laryngeal toxicity occurred in 10.3% versus 9.8% and 6.8% versus 11.8% of patients receiving cisplatin-radiotherapy versus cetuximab, respectively. Conclusions No significant difference in LEDFS was observed between the two arms. TPF-ICT followed by conventional chemoradiotherapy or cetuximab was feasible, and long-term toxicity was not statistically different between the two arms. LEDFS appears as a relevant end-point. (C) 2020 Elsevier Ltd. All rights reserved.