LBA37 - Final results: Randomized assessment of cisplatin dosing interval for ototoxicity (RADIO) trial comparing chemoradiation (CRT) with cisplatin q3weekly to weekly for locally advanced squamous cell carcinoma of the head and neck (LASCCHN)

Background

Most patients (pts) with HPV-related oropharyngeal cancer will be cured and live with longterm adverse effects of their treatment. We tested the hypothesis of less permanent hearing loss with cisplatin given weekly versus q3weekly with RT for LASCCHN in a randomized clinical trial.

Methods

Eligible adult LASCCHN pts were planned for curative intent CRT, considered suitable for q3weekly cisplatin and had adequate baseline hearing. RT included 70 Gy/35 fractions to areas of gross disease. Pts were randomized to concurrent cisplatin either 100 mg/m² days 1, 22 and 43 or 40 mg/m² weekly x 7 weeks. Co-primary endpoints were the incidence of ≥grade 2 audiometrically measured hearing impairment and hearing-related QoL, both measured at 1 year. All pts provided informed consent for this REB approved trial.

Results

99 eligible pts (85 males/14 females) median age 61 years (range, 40-75 years) were enrolled at 3 academic cancer centers in Canada between Feb 2019 and June 2023. Baseline pt characteristics were well balanced. 94% of pts had p16-positive oropharyngeal cancer. 50 pts received cisplatin q3weekly for 3 (74%), 2 (22%) or 1 cycle (4%); and 49 pts received weekly cisplatin for a median of 6 cycles (range, 3-7); with similar mean cisplatin doses. Grade 3/4 acute toxicities occurred in 40% and 47% of pts, respectively. 47 pts were alive at 1-year in each arm and 1-year audiograms were available for 87 pts (93%). Hearing impairment >grade 2 at 1 year was present in 32 pts (64.0%) treated with q3weekly cisplatin and 20 pts (40.8%) treated with weekly cisplatin (p=0.027). The incidence of tinnitus (92.0% vs 73.5%, p=0.017) and need for hearing amplification (54.0% vs 36.7%, p=0.11) were higher with q3weekly cisplatin.

Conclusions

Grade 2/3 hearing impairment at 1 year was reduced by 40% with the use of weekly cisplatin given concurrent with RT compared to a q3weekly schedule. Rates of tinnitus and the need for hearing amplification were also reduced. Hearing-related QoL data were collected and will also be presented. Our results support the use of weekly cisplatin in pts with HPV-related LASCCHN to reduce longterm hearing morbidity.

Clinical trial identification

NCT03649048.

Editorial acknowledgement

Legal entity responsible for the study

M. S. Kuruvilla.

Funding

Academic Medical Organization of Southwestern Ontario Innovation Fund, Medical Oncology Research Fund London Regional Cancer Program, Juravinski Hospital and Cancer Centre Foundation. and The John Rogerson Jackson and Dorothea Marguerite Jackson Medical Research Fund.

Disclosure

E. Winquist: Financial Interests, Personal, Advisory Board: Bayer, Eisai, EMD Serono, Ipsen; Financial Interests, Personal and Institutional, Advisory Board, Clinical trial funding: Merck, Roche/Genetech; Financial Interests, Institutional, Advisory Board, Clinical trial funding: Novartis. All other authors have declared no conflicts of interest.