Docetaxel as a radiosensitiser in cisplatin-ineligible patients with head and neck cancer
Systemic therapy options have not been systematically evaluated in cisplatin-ineligible locally advanced head and neck squamous cell carcinoma (LAHNSCC) patients undergoing chemoradiation. A novel phase III study therefore evaluated docetaxel as a radiosensitiser in this setting. The addition of docetaxel to radiation improved disease-free survival and overall survival in cisplatin-ineligible LAHNSCC and as such represents a new standard of care.
Cisplatin-based chemoradiotherapy is a standard treatment option for patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC). Unfortunately however, many patients are not suitable to receive cisplatin but prospective data to assist in treatment planning in this setting are very limited. With docetaxel, promising results were obtained in phase I and II studies and docetaxel can be administered in most cisplatin unsuitable situations. Therefore, a phase III study was initiated.
Study Design
This was a randomised, open-label, phase III study. Adults with LAHNSCC planned for radical or adjuvant chemoradiation, with an ECOG performance status 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/m2 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 two-year disease-free survival (DFS) and key secondary endpoints were two-year overall survival (OS), adverse events and quality of life (Trial outcome index [TOI]).
Results
The study recruited 356 patients in which 176 were randomised to the RT arm and 180 to the docetaxel-RT arm. Patients were well balanced in terms of baseline characteristics between the two arms. The majority of patients (i.e. a third of the patients) had oral cavity primaries. Of note, about 16% of patients in both arms were over the age of 70 years. The majority of patients had stage IVA disease. A quarter of the patients were ineligible because of a low creatinine clearance, approximately 40% of patients had sensorineural hearing loss and approximately 40% of patients had ECOG performance status of two. Compliance to radiation was excellent, with over 90% of patients receiving the full radiation dose. In the docetaxel-arm, there were radiation interruptions in 11.1% of the patients (vs. 6.2% in the RT arm). Approximately 80% of patients received two-dimensional radiotherapy. The median number of docetaxel cycles was 6 and 85.6% of patients received at least 5 cycles.
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. There was a significantly higher incidence of grade 3 and above mucositis (22.2% vs. 49.7%; p< 0.001), odynophagia (33.5% vs. 52.5%; p< 0.001) and dysphagia (33% vs. 49.7%; p< 0.002) with the addition of docetaxel. With regard to laboratory abnormalities, only hyponatremia was significantly worse after the addition of docetaxel. The two-year DFS was 30.3% versus 42% in the RT and docetaxel-RT arms, respectively (HR[95%CI]: 0.673[0.521-0.868], p= 0.002). The median OS was 15.3 months in the RT arm and 25.5 months in the docetaxel-RT arm. The two-year OS was 41.7% versus 50.8% in the RT and docetaxel-RT arms, respectively (HR[95%CI]: 0.747[0.569-0.98], p= 0.035). The benefit of docetaxel was consistent across all the pre-planned subgroups. Finally, the addition of docetaxel did not lead to a worsening of TOI scores and FACT-G scores at 6 months.
Conclusion
The addition of docetaxel to radiotherapy improved both the disease-free survival and the overall survival in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma. This now represents a new reference standard of care for cisplatin-ineligible patients planned for chemoradiotherapy.
Reference
Patil VM, et al. 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. Presented at ASCO 2022; Abstract LBA6003.
