Phase I study of induction chemotherapy with afatinib, ribavirin, and weekly carboplatin and paclitaxel for stage IVA/IVB human papillomavirus‐associated oropharyngeal squamous cell cancer.

Abstract: Background: The human papillomavirus (HPV) E6 oncoprotein enhances the oncogenic potential of ErbB proteins in HPV‐related malignancies. This phase I study evaluates the addition of afatinib, an ErbB family inhibitor, and ribavirin to paclitaxel and carboplatin induction chemotherapy in HPV‐associated, locally advanced oropharyngeal squamous cell carcinoma (SCC). Methods: This dose escalation study included 2 doses of oral afatinib: 30 and 40 mg daily. Ribavirin dosing was weight based. Paclitaxel (80 mg/m²) and carboplatin (area under the curve [AUC] 1.5) were administered on days 1 and 8 of each 21‐day cycle. After 3 cycles, patients were removed from protocol to receive definitive treatment. Results: Among 10 patients, there were no dose‐limiting toxicities. Six patients (67%) had unconfirmed objective partial responses. The 2‐year progression‐free survival rate was 75%. Conclusion: Afatinib, ribavirin, paclitaxel, and carboplatin induction chemotherapy is safe and well tolerated. The phase II recommended dose of afatinib is 40 mg oral daily in this combination regimen. [ABSTRACT FROM AUTHOR]