A Phase 1 Study of Afatinib in Combination with Postoperative Radiation Therapy with and Without Weekly Docetaxel in Intermediate- and High-Risk Patients with Resected Squamous Cell Carcinoma of the Head and Neck.

Purpose: To determine the maximum tolerated dose and tolerability of (1) afatinib in combination with postoperative radiation therapy (PORT) for patients with intermediate-risk squamous cell carcinoma of the head and neck (SCCHN) and (2) afatinib in combination with PORT and weekly docetaxel for high-risk SCCHN.

Methods And Materials: An open-label, multicenter, 2-cohort, phase 1 dose-escalation trial was conducted using a 3 + 3 design. Eligible patients had definitive surgery for SCCHN, including the oral cavity, oropharynx, larynx, or hypopharynx and had intermediate- or high-risk pathologic features. Afatinib was given for a 1-week lead in before PORT and daily during 6 to 6.5 weeks of PORT with or without weekly docetaxel. The starting dose was 30 mg and could be escalated to 40 mg or de-escalated to 20 mg. The primary objective was to determine the maximum tolerated dose of afatinib with PORT or PORT + docetaxel.

Results: Between April 2013 and November 2017, 27 patients were enrolled and started study treatment, including 16 intermediate-risk patients and 11 high-risk patients, all with Eastern Cooperative Oncology Group performance status of 0 to 1. Most patients (n = 25) had oral cavity cancer and were treated to a median total dose of 60 Gy in the intermediate-risk arm and 65 Gy in the high-risk arm. There was 1 grade 4 event, but no deaths. The maximum tolerated dose was not established owing to dose-limiting toxicities (DLTs) in both arms. In the high-risk arm, DLTs were grade 3 mucositis (n = 3) and grade 3 diarrhea/hypokalemia (n = 1). In the intermediate-risk arm, DLTs were grade 3 mucositis (n = 4) and grade 3 diarrhea (n = 2).

Conclusions: Afatinib in combination with PORT for mucosal SCCHN was difficult to tolerate because of grade 3 toxicity, mostly mucositis, in a cohort of patients requiring high-dose PORT to the oral cavity. This regimen may be better tolerated for a non-oral cavity site or if given in a different schedule.