Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation Therapy for Locoregionally Advanced Head and Neck Cancer: HPV-negative Subset Analysis

Abstract

detection of recurrence were abstracted. Patients either received definitive RT alone (nZ38, 15.4%) or concurrent systemic therapy and RT (nZ209, 84.6%). Outcomes, including local control (LC), regional control (RC), locoregional control (LRC), freedom from distant metastases (FFDM), and overall survival (OS) were calculated according to Kaplan-Meier method from the end of RT. Patients received a 3-month posttreatment positron emission tomographic/computed tomographic (PET/CT) scan and were seen every 3 months in the first year, every 4 months in Year 2, and every 6 months in Years 3 to 5. Results: Median follow-up of all patients was 36 months. LC was achieved in 239 of 245 patients, with a 3-year LC rate of 97.8%. Of the 6 local failures, all were detected by direct visualization (nZ2) or flexible laryngoscopy (nZ4). Three-year RC was 95.3%, where patients with 5 nodes or level 4 lymph nodes present were more likely to suffer regional failure (P<.05). Of the 9 regional recurrences, 89% (nZ8) were found by symptoms or 3-month posttreatment PET/CT. Three-year LRC was 94%. Of the 13 patients that suffered a locoregional failure, 92% (nZ12) presented with either symptoms or persistent disease on 3-month posttreatment PET/CT. Three-year FFDM rate was 91.4%, with increased risk of metastases occurring in patients with a lymph node greater than 6 cm, bilateral lymphadenopathy, 5 or more nodes, or if a lymph node was present in level 4 (P<.05). Of the 21 patients who suffered distant recurrence, 71% (nZ15) were found due to symptoms or 3-month posttreatment imaging. Three-year OS was 91% for all patients. Late grade 3 toxicity occurred in 21 patients (9%), with 19 being grade 3 toxicities and 2 grade 4 toxicities. The majority of toxicity and/or failure occurred within the first 6 months (64%), with only 4 events beyond 2 years. Conclusion: HPV-associated oropharyngeal cancer treated with definitive RT has excellent outcomes. Of the few patients that suffered a local failure, all were identified with physical exam. Symptoms and/or 3-month posttreatment PET/CT identified 92% of locoregional failures and 71% of distant failures. Given these findings, if posttreatment of PET/CT is negative, no further imaging is warranted. Follow-up should include history and physical exam with direct visualization. Author Disclosure: J.M. Frakes: None. A.O. Naghavi: None. T. Strom: None. A.R. Giuliano: None. L.B. Harrison: None. A. Trotti: None. J.J. Caudell: None.