Phase II trial of bevacizumab + cetuximab + cisplatin with concurrent intensity‐modulated radiation therapy for patients with stage III/IVB head and neck squamous cell carcinoma

Abstract

Background To evaluate the efficacy and tolerability of the addition of two monoclonal antibodies, bevacizumab and cetuximab, to two cycles of high-dose cisplatin administered concurrently with IMRT for HNSCC. Methods Patients with newly diagnosed stage III/IVB (M0) HNSCC received cetuximab (400 mg/m2 loading dose, followed by 250 mg/m2 weekly), bevacizumab (15 mg/kg, days 1 and 22), and cisplatin (50 mg/m2, days 1, 2, 22, and 23) concurrently with IMRT (70 Gy). The primary endpoint was progression free survival (PFS). Secondary endpoints were overall survival (OS) and safety and tolerability. Results Among 30 patients enrolled, the primary tumor site was oropharynx in 25 patients (p16 immunohistochemistry was positive in 17, negative in 1, and not done in 6 of the oropharynx tumors). Median age was 57 years (range, 38–77 years) and 27 patients had clinical stage IVA disease. All patients completed the full planned dose of radiation therapy. The most common ≥ grade 3 adverse events were lymphopenia, mucositis (functional), and dysphagia. With a median follow up of 33.8 months, 2 year PFS was 88.5% (95% CI, 68.1–96.1) and 2 year OS was 92.8% (95% CI, 74.2–98.1%) Conclusion The addition of bevacizumab and cetuximab to two cycles of cisplatin, given concurrently with IMRT, was well tolerated and was associated with favorable efficacy outcomes in this patient population.

Frizzled2 mediates the migration and invasion of human oral squamous cell carcinoma cells through the regulation of the signal transducer and activator of transcription-3 signaling pathway

“…In accordance with previous studies (5), an earlier epidemiological analysis for patients with oral cancers in China has shown that over a half of the examined oral malignancies are SCC (6), suggesting SCC as the predominate oral malignancy. Despite recent advances in novel therapies (7), the prognosis for patients with OSCC remains poor (8). Thus, it is imperative to identify a novel therapeutic target in OSCC.…”

Immunotherapy for Head and Neck Squamous Cell Carcinoma

“…Most recently, a phase II study of the addition of Bevacizumab to Cisplatin plus intensity modulated radiation therapy (IMRT) did not show any significant increase in toxicity, with a 2 year PFS rate of 76% and overall survival rate of 88% 54 . With the addition of Cetuximab to the above regimen, the same authors showed an improved progression free survival to 89% and overall survival to 93% 55 . Cetuximab and bevacizumab have also been evaluated together in recurrent or metastatic HNSCC and showed tumor growth inhibition both in vitro and in vivo , and in the clinical trial showed a disease control rate of 73% and OS of 7.5 months 56 .…”

Radiotherapy plus EGFR inhibitors: synergistic modalities

“…Several clinical studies have yielded positive results when using a combination of bevacizumab, cetuximab, and chemotherapy in addition to radiation or when adding bevacizumab to the combination of erlotinib, chemotherapy, and radiation [17][18][19]. Further exploration of these combined strategies and their safety profiles thus seems like a promising direction to pursue.…”