Phase III Randomized Trial of Chemotherapy With or Without Bevacizumab in Patients With Recurrent or Metastatic Head and Neck Cancer

Abstract

PURPOSE We evaluated the addition of bevacizumab, a humanized monoclonal antibody that targets vascular endothelial growth factor, to platinum-based chemotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Patients with chemotherapy-naïve (or with prior platinum as part of multimodal therapy completed ≥ 4 months earlier) recurrent or metastatic SCCHN were randomly assigned to receive a platinum-based chemotherapy doublet with or without bevacizumab 15 mg/kg given intravenously every 3 weeks until disease progression. Chemotherapy could be discontinued after six cycles if a maximum response was achieved. RESULTS The study randomly assigned 403 patients. Median overall survival (OS) was 12.6 months with bevacizumab plus chemotherapy (BC) and 11.0 months with chemotherapy alone (hazard ratio, 0.87; 95% CI, 0.70 to 1.09; P = .22). At 2, 3, and 4 years, the OS rates were 25.2% v 18.1%, 16.4% v 10.0%, and 11.8% v 6.4% for BC versus chemotherapy, respectively. In an analysis of 365 eligible patients who started treatment, the hazard ratio was 0.82 (95% CI, 0.65 to 1.04; P = .10), with a median OS of 14.2 months on BC v 11.1 months on chemotherapy. Median progression-free survival with BC was 6.0 months v 4.3 months with chemotherapy ( P = .0014). Overall response rates were 35.5% with BC and 24.5% with chemotherapy ( P = .016). There was increased toxicity, including a higher rate of treatment-related grade 3 to 5 bleeding events (6.7% v 0.5%; P < .001) and treatment-related deaths (9.3% v 3.5%; P = .022) with BC versus chemotherapy. CONCLUSION The addition of bevacizumab to chemotherapy did not improve OS but improved the response rate and progression-free survival with increased toxicities. These results encourage biomarker-driven studies of angiogenesis inhibitors with better toxicity profiles in select patients with SCCHN.

Immune-checkpoint inhibitor plus chemotherapy versus conventional chemotherapy for treatment of recurrent or metastatic head and neck squamous cell carcinoma: a systematic review and network meta-analysis

“…In total, 431 studies were identified through database search and 186 additional studies were identified through trial registers, international conferences, references of reviews, and other sources. Twenty RCTs 5 – 7 , 10 , 19 – 34 with full texts and six with abstracts only 9 , 35 – 39 met the eligibility for assessment ( Figure 1 ). The amount of evidence included is illustrated using a network diagram ( Figure 2A , 3A ).…”

Serum and tissue expression of neuropilin 1 in precancerous and malignant vocal fold lesions

“…metastatic SCC of the head and neck, did not demonstrate efficacy in increasing overall survival but improved the response rate and progression-free survival [24]. These results encourage further biomarker-driven studies to identify other more effective angiogenesis inhibitors.…”

“…The results of meta-analysis that included 12 studies comprising 1002 patients showed that overexpression of VEGF receptor (VEGFR) in 90% of head and neck squamous cell carcinomas (SCC) and the up-regulation of VEGFR was associated with poorer survival outcomes [ 23 ]. However the results of currently performed trials analyzing the addition of bevacizumab, a monoclonal antibody targeting VEGF, to platinum-based chemotherapy in recurrent or metastatic SCC of the head and neck, did not demonstrate efficacy in increasing overall survival but improved the response rate and progression-free survival [ 24 ]. These results encourage further biomarker-driven studies to identify other more effective angiogenesis inhibitors.…”

Vascular Endothelial Growth Factor: A Translational View in Oral Non-Communicable Diseases

“…A recent phase III clinical trial which evaluated the addition of bevacizumab to platinum-based chemotherapy in recurrent or metastatic SCCHN, showed that the addition of bevacizumab did not improve overall survival but did improve response rate and progression-free survival. Nevertheless, there was a significant increase in toxicity, including bleeding events and treatment related deaths [ 79 ].…”