Randomized Phase 2 Trial of Stereotactic Body Radiation Therapy (SBRT) and Concurrent and Adjuvant Cetuximab vs Cetuximab and Docetaxel in Recurrent, Previously Irradiated Squamous Cell Carcinoma of the Head and Neck.

The treatment of recurrent head and neck cancer presents a significant challenge in previously irradiated patients. Therapeutic options in this patient population tend to be limited and are often associated with severe toxicity and decreased efficacy compared with front line therapies. Stereotactic body radiation therapy (SBRT) is a salvage technique that provides highly conformal, ablative doses to tumor while minimizing exposure of the surrounding organs at risk. The precise role of concurrent systemic therapy with SBRT, though, remains unclear and is a topic of active investigation. We conducted a randomized, phase 2 trial exploring the addition of docetaxel to concurrent and adjuvant cetuximab with head and neck SBRT in patients with recurrent or second primary head and neck cancers. Inclusion criteria included patients ages ≥18, ECOG 0-1 with squamous cell carcinoma of the head and neck arising within an area previously receiving a dose of at least 50 Gy. Patients were randomized to receive 44-50 Gy/5 fraction SBRT with concurrent and adjuvant cetuximab (control arm) vs the same regimen with the addition of concurrent and adjuvant docetaxel (experimental arm) and were stratified by prior cetuximab exposure. The primary objective was evaluation of 1-year locoregional progression-free survival (LRPFS) with secondary endpoints consisting of progression free survival (PFS), overall survival (OS) and toxicity assessment. The study was designed as a superiority trial to detect a 20% improvement in LRPFS in the experimental arm. Using a power of 85% at a significance level of 0.10, the estimated sample size was 92 patients randomized in a 1:1 manner. The trial was halted due to slow accrual after a total of 38 patients (19 in each arm) had been randomized. No difference was observed in 1-year LRPFS between the control and experimental arms (36% vs 37%, p=0.63). There were similar rates of 1-year PFS in both arms (36% vs 32%, p=0.92) with a non-significant difference in 1-year OS (46% vs 20%, p=0.20) favoring the control arm. There was no difference in the rates of grade 3+ toxicity which was 84% in both arms (p=0.99) although there were twice as many grade 5 events in the docetaxel arm (n=4 vs 2). Although underpowered, we did not observe an improvement in LRPFS, PFS or OS with the addition of docetaxel to concurrent and adjuvant cetuximab and SBRT for recurrent head and neck squamous cell carcinomas in previously irradiated patients. The relatively poor disease control and high degree of toxicity observed in both arms presents an ongoing challenge in the management of this patient population. [ABSTRACT FROM AUTHOR]