Phase II Trial of De-Intensified Chemoradiotherapy for Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma

Abstract

Purpose: To report the results of a phase II clinical trial of de-intensified chemoradiotherapy for patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma.

Materials and methods: Major inclusion criteria were (1) having American Joint Committee on Cancer (AJCC) 7th edition T0-T3, N0-N2c, M0 (AJCC 8th edition T0-T3, N0-N2, M0), (2) being p16 positive, and (3) reporting minimal or remote smoking history. Treatment was limited to 60 Gy intensity-modulated radiotherapy with concurrent intravenous cisplatin 30 mg/m² once per week. Patients with T0-T2 N0-1 (AJCC 7th edition) did not receive chemotherapy. All patients had a 10- to 12-week post-treatment positron emission tomography/computed tomography to assess for neck dissection. The primary end point was 2-year progression-free survival. Secondary end points included 2-year local-regional control, distant metastasis-free survival and overall survival, and patient-reported outcomes (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events).

Results: One hundred fourteen patients were enrolled (median follow-up of 31.8 months), with 81% having a minimum follow-up of 2 years. Eighty percent of patients had 10 or fewer tobacco pack-years. Two-year local-regional control, distant metastasis-free survival, progression-free survival, and overall survival were as follows: 95%, 91%, 86%, and 95%, respectively. Mean pre- and 2-year post-treatment European Organisation for Research and Treatment of Cancer quality of life scores were as follows: global, 79/84 (lower worse); swallowing, 8/9 (higher worse); and dry mouth, 14/45 (higher worse). Mean pre- and 2-year post-treatment patient-reported outcomes version of the Common Terminology Criteria for Adverse Events scores (0 to 4 scale, higher worse) were as follows: swallowing, 0.5/0.7, and dry mouth, 0.4/1.3. Thirty-four percent of patients required a feeding tube (median, 10.5 weeks; none permanent). There were no grade 3 or higher late adverse events.

Conclusion: Clinical outcomes with a de-intensified chemoradiotherapy regimen of 60 Gy intensity-modulated radiotherapy with concurrent low-dose cisplatin are favorable in patients with human papillomavirus-associated oropharyngeal squamous cell carcinoma. Neither neoadjuvant chemotherapy nor routine surgery is needed to obtain favorable results with de-escalation.

Trial registration: ClinicalTrials.gov NCT02281955.

FIG 1.

Kaplan-Meier curves for (A) local-regional control (LRC), (B) distant metastasis-free survival (DMFS), (C) progression-free survival (PFS), and (D) overall survival (OS). Two-year LRC, DMFS, PFS, and OS were 95% (95% CI, 88.6% to 97.9%), 91% (95% CI, 83.9% to 95.4%), 86% (95% CI, 77.5% to 91.3%), and 95% (95% CI, 89.3% to 98.1%), respectively. Three-year LRC, DMFS, PFS, and OS were 94% (95% CI, 96.5% to 97.2%), 91% (95% CI, 83.4% to 95.4%), 85% (95% CI, 76.0% to 90.3%), and 95% (95% CI, 89.3% to 98.1%), respectively.

FIG 2.

(A) European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30 responses (mean scores) for global health status and EORTC QLQ H&N35 responses (mean scores) for selected symptoms. (B) Patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE; mean scores) for selected symptoms. tx, treatment.