Results of phase 3 randomized trial for use of docetaxel as a radiosensitizer in patients with head and neck cancer unsuitable for cisplatin-based chemoradiation.

LBA6003 Background: Systemic therapy options have not been systematically evaluated in cisplatin-ineligible locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients undergoing chemoradiation. This study evaluated docetaxel as a radiosensitizer in this setting. Methods: This was a randomised open-label study. Adults with LAHNSCC planned for radical or adjuvant chemoradiation, with ECOG PS 0-2 and who were cisplatin-ineligible as per the criteria by Ahn et al were enrolled. The patients were randomly assigned 1:1 to receive radiation alone or radiation with concurrent docetaxel 15 mg/m 2 weekly for a maximum of 7 cycles. Adverse events were recorded in accordance with CTCAE version 4.03. The FACT-G, and H and N questionnaires (version 4) were self-administered at baseline, 6 months, 12 months and at 24 months. The primary endpoint was disease-free survival (DFS) and key secondary endpoints were overall survival (OS), adverse events and quality of life (Trial outcome index (TOI)). Results: The study recruited 356 patients with 176 in RT and 180 in the docetaxel-RT arm. The 2-year DFS was 30.3% (95%CI 23.6-37.4) versus 42% (95%CI 34.6-49.2) in the RT and docetaxel-RT arms respectively (Hazard ratio- 0.673; 95% CI 0.521-0.868; P-value=0.002). The median overall survival (OS) was 15.3 months (95%CI 13.1-22) in the RT arm and 25.5 months (95% CI 17.6-32.5) in the docetaxel-RT arm. (Log-rank P-value =.0.035). The 2 -year OS was 41.7% (95%CI 34.1-49.1) versus 50.8% (95%CI 43.1-58.1) in the RT and docetaxel-RT arms respectively (Hazard ratio-0.747; 95% CI 0.569-0.98; P-value=0.035). Any grade 3 or above adverse events were seen in 102 patients (58%) in RT and in 146 (81.6%) in docetaxel-RT arms respectively (P-value=0.000). There was a higher incidence of grade 3 and above mucositis (22.2% versus 49.7%; P<0.001), odynophagia (33.5% versus 52.5%; P<0.001) and dysphagia (33% versus 49.7%; P<0.002) with the addition of docetaxel. The addition of docetaxel did not lead to a worsening of TOI scores and FACT-G scores at 6 months. Conclusions: The addition of docetaxel to radiation improved disease-free survival and overall survival in cisplatin-ineligible LAHNSCC and represents a new standard of care. Clinical trial information: CTRI/2017/05/008700.