Phase II randomized trial of radiation therapy, cetuximab and pemetrexed with or without bevacizumab in patients with locoregionally-advanced head and neck cancer.

Phase II randomized trial of radiation therapy, cetuximab and pemetrexed with or without bevacizumab in patients with locoregionally-advanced head and neck cancer.

Ann Oncol. 2016 May 13;

Authors: Argiris A, Bauman JE, Ohr J, Gooding WE, Heron DE, Duvvuri U, Kubicek GJ, Posluszny DM, Vassilakopoulo M, Kim S, Grandis JR, Johnson JT, Gibson MK, Clump DA, Flaherty JT, Chiosea SI, Branstetter B, Ferris RL

Abstract
BACKGROUND: We previously reported the safety of concurrent cetuximab, an antibody against epidermal growth factor receptor (EGFR), pemetrexed and radiation therapy (RT) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In this non-comparative phase II randomized trial, we evaluated this non-platinum combination with or without bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF).
PATIENTS AND METHODS: Patients with previously untreated stage III-IVB SCCHN were randomized to receive: conventionally fractionated radiation (70Gy), concurrent cetuximab, and concurrent pemetrexed (arm A); or the identical regimen plus concurrent bevacizumab followed by bevacizumab maintenance for 24 weeks (arm B). The primary endpoint was 2-year progression-free survival (PFS), with each arm compared to historical control. Exploratory analyses included the relationship of established prognostic factors to PFS and quality of life (QOL).
RESULTS: Seventy-eight patients were randomized: 66 oropharynx (42 HPV-positive, 15 HPV-negative, 9 unknown) and 12 larynx; 38 (49%) had heavy tobacco exposure. Two-year PFS was 79% (90% CI 0.69 - 0.92; p<0.0001) for arm A and 75% (90% CI 0.64 - 0.88; p<0.0001) for arm B, both higher than historical control. No differences in PFS were observed for stage, tobacco history, HPV status, or type of center (community versus academic). A significantly increased rate of hemorrhage occurred in arm B. SCCHN-specific QOL declined acutely, with marked improvement but residual symptom burden one year post-treatment.
CONCLUSIONS: RT with a concurrent non-platinum regimen of cetuximab and pemetrexed is feasible in academic and community settings, demonstrating expected toxicities and promising efficacy. Adding bevacizumab increased toxicity without apparent improvement in efficacy, countering the hypothesis that dual EGFR-VEGF targeting would overcome radiation resistance and enhance clinical benefit. Further development of cetuximab, pemetrexed and RT will require additional prospective study in defined, high-risk populations where treatment intensification is justified.

PMID: 27177865 [PubMed - as supplied by publisher]

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