Initial Results from a Phase 2 Prospective Trial of De-intensified Chemoradiation therapy for Low-Risk HPV-associated Oropharyngeal Squamous Cell Carcinoma

Abstract

To report initial results from a prospective phase 2 clinical trial of highly de-intensified chemoradiation therapy (CRT) for patients with favorable risk HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). The major inclusion criteria were: 1) T0-T3, N0-N2c, M0, 2) HPV or p16 positive, and 3) minimal/remote smoking history. Treatment was limited to 60 Gy intensity modulated radiation therapy with concurrent weekly intravenous cisplatin 30 mg/m2 (second choice was cetuximab). Patients received neither induction chemotherapy nor definitive surgery. Patients with T0-T2 N0-1 disease did not receive chemotherapy (i.e. received 60 Gy alone). All patients had a 10- to 12-week posttreatment PET/CT to determine need for planned neck dissection. The primary study endpoint is 2-year progression-free survival (PFS). Secondary endpoint measures include 2-year local control (LC), regional control (RC), distant metastasis free survival (DMFS), and overall survival (OS), and patient reported symptoms (PRO-CTCAE) and quality of life (EORTC QLQ-C30 & H&N35). Data analysis was performed for patients with a minimum of 1 year of follow-up. One hundred and thirteen patients have enrolled, with 82 having a minimum follow-up of 1 year. Smoking status was as follows: 49% never, 35% ≤ 10 pack-years, and 16% > 10 pack-years. Forty-four percent were HPV and p16 positive and 56% were HPV negative/unknown and p16 positive. Posttreatment PET/CT complete response rate was 97% at the primary site and 81% in the neck. Eight patients had planned neck dissection with 1 having pathological residual disease. Twoyear PFS, LC, RC, DMFS, CSS, and OS are the following: 93%, 98%, 99%, 95%, 96%, and 95%. Sixteen patients were treated with RT alone and all remain in cancer control. Mean pre- and 1-year posttreatment EORTC QOL scores were: Global 79/82 (lower worse), Swallowing 8/12 (higher worse), Dry Mouth 15/55 (higher worse), and Sticky Saliva 10/33 (higher worse). Of all patients, 39% patients required a feeding tube (none permanent) for a median of 10.5 weeks (range 3-42 weeks). Mean pre- and 1-year posttreatment PRO-CTCAE (0 to 4 scale, higher worse) scores were: Swallowing 0.5/0.9 and Dry mouth 0.5/1.6. There were no ≥ Grade 3 late adverse events. Initial clinical outcomes with highly de-intensified CRT are excellent in favorable risk OPSCC with evidence of better preservation of quality of life compared to standard therapies (ClinicalTrials.gov, NCT02281955).