Session Item

CompARE is a phase III randomised controlled trial using an adaptive, multi-arm multi-stage design to evaluate alternative regimes for escalating treatment of intermediate and high risk oropharyngeal cancer (OPC). This paper presents the first results of the investigational arm evaluating biological effective dose escalated accelerated hypofractionated chemoradiation.

Patients with Intermediate-risk OPC (HPV positive N2b or above disease and greater than 10 pack year history of smoking), or high-risk OPC (HPV negative), aged 16-70 years with ECOG PS 0-1 and suitability for concurrent chemoradiotherapy were randomised (2:1) to standard therapy in arm 1 using 70Gy in 35 fractions with concurrent cisplatin or one of several experimental arms. Arm 3 reported here evaluated 64Gy in 25 fractions with concurrent cisplatin delivered over 5 weeks. All centres participated in a central radiotherapy quality assurance programme and all patients had central HPV evaluation. Primary outcome was overall survival (OS) with an interim outcome of event free survival (EFS). 72 control arm events are required to perform the first interim analysis. Secondary outcome measures included toxicity (CTCAEv4.0), QoL, swallowing using MDADI questionnaire and gastrostomy dependence. Analysis was by intention to treat. 

257 patients (172 in Arm 1 and 85 in Arm 3) were recruited across 27 centres and eligible for this analysis. Recruitment was suspended to this comparator arm in advance of planned interim analyses due to a SAE. Baseline characteristics were well balanced between the arms with 80% of patients having intermediate risk OPC and 20% with high risk. 97% patients received radiotherapy as planned for each arm. Overall median length of follow up was 36.7 months (95% CI. 27.6, 37.5). Three-year EFS rate was 72% (95%CI 64-78%) in arm 1 and 68% (95% CI 56-78%) in arm 3, (p=0.98). Adjusted hazard ratio for arm 3 versus 1 was 1.00 (95/% CI 0.62, 1.62). Three-year OS rate was 79% (95%CI 71-86%) in arm 1 and 74% (95%CI 62-83%) in arm 3, (p=0.59). Adjusted hazard ratio for arm 3 versus 1 was 1.17 (95% CI 0.66, 2.05). The proportional-hazards model was not violated. Rates of gastrostomy tube use at 2 years were 5% and 9% in arms 1 and 3 respectively (p=0.35). 

Biological effective dose escalated chemoradiation did not appear to demonstrate any benefit over standard therapy in patients with intermediate and high risk OPC. The CompARE trial continues to recruit and evaluate other regimes. 

Reporting of the outcomes of harms and quality of life are the subject of a separate abstract to this meeting.