Session Item

CompARE is an adaptive, multi-arm multi-stage phase III RCT to evaluate alternative regimens for escalating treatment of intermediate and high-risk oropharyngeal cancer (OPC). This paper presents harms and QoL results for the comparison of dose escalated accelerated hypofractionated chemoradiation (arm 3) vs. control.

Patients 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 evaluated 64Gy in 25 fractions with concurrent cisplatin delivered over 5 weeks. Harms were recorded using CTCAEv4.0 with mucositis being clinician scored. QoL was assessed using standard validated questionnaires; EORTC QLQ-C30 and the Head and Neck cancer specific module HN35 provide detailed function and symptom scores, EQ-5D-5L provides a utility valuation for patient health state and an EQ- VAS score. The MDADI questionnaire provides a composite score for swallowing outcomes. QoL booklets were completed at Baseline, End of Treatment and 3, 6, 12, 18, and 24 months follow up. Clinically relevant harms data were classed as acute; on treatment and follow up to 3 months, or late; defined as beyond 3 months. 

257 patients (172 in Arm 1 and 85 in Arm 3) were recruited across 27 centres for this comparison. Recruitment was suspended to this comparator arm in advance of planned interim analyses due to a SAE.

There were 221 (142 arm 1 and 79 arm 3) reported SAEs for this comparison in 131 patients, 88 arm 1 (51%) and 43 arm 3 (51%) of which there were 4 SUSARs reported; 3 Fatal/Life threatening (1 arm 1, 2 arm 3) and 1 non-fatal/life threating. Acute harms ≥ Grade 3 (G3) reported include; dysphagia (arm 1 52%, arm 3 56%, p=0.475) Oral Mucositis (48% vs. 69%, p=0.001). Late harms ≥G3 reported include; dry mouth (arm 1 6%, arm 3 11%, p=0.169) dysphagia (arm 1 13%, arm 3 18%, p=0.364) oral mucositis (3% vs. 4%, p=0.787).

Of the 257 randomised patients, 254 (99%) completed at least one QoL booklet. Currently 1305 booklets have been received (863 control vs 442 experimental) with a median of 6 forms for both arms. The QoL booklet completion rate at baseline was 93%. There was a trend towards worse scores in arm 3 on follow up for swallowing, social eating, opening mouth, and specific H&N pain. There was no difference between the arms for the Global Health status score, the EQ5D-5L utility score and the patient reported EQ VAS. On follow up dose escalated chemoradiation arm patients consistently reported worse MDADI composite score circa 5 points. 

An increased incidence of acute mucositis was reported when using dose escalated chemoradiation. Although there was no significant difference in reported late toxicity, some QoL domain scores were worse in the dose escalated arm. The CompARE trial continues to recruit and evaluate other regimens.

Reporting of the survival outcomes of the trial are the subject of a separate abstract to this meeting