The NRG Oncology NRG-HN005 phase II/III clinical trial did not meet the non-inferiority criteria to proceed to the phase III portion of the study.

The phase II portion of the NRG-HN005 evaluated two experimental treatment arms against a control arm for patients with p16-positive (p16+, accepted as a surrogate for HPV+ status), locoregionally advanced oropharyngeal cancer.

The interim futility results were recently reported during the Plenary Session of the American Society for Radiation Oncology Annual Meeting in Washington, DC.

“This study, despite the overall failure of the experimental arms, is extremely important as an affirmation that this group of patients achieves genuinely outstanding outcomes with traditional chemoradiation. Furthermore, as shown by the incredibly good prognosis of patients in the control arm, this study sets a new very high bar for deintensification studies in the future.” stated Sue S. Yom, MD, PhD, of the University of California San Francisco and the lead author of the NRG-HN005 abstract.

NRG-HN005 compared standard dose, slightly accelerated intensity modulated radiotherapy (IMRT) and 2 cycles of cisplatin chemotherapy given every 3 weeks to a lower dose of IMRT with the same cisplatin schedule or slightly accelerated IMRT with 6 cycles of the immunotherapy drug nivolumab given before, during, and after radiation.

The control arm dose and schedule for the IMRT and cisplatin regimen stemmed from the findings in the RTOG 1016 clinical trial which deemed radiotherapy and cisplatin to be the standard of care for patients with p16-positive oropharyngeal cancer.

The primary aim of the phase II portion of this study was to determine if the lower dose IMRT combined with either chemotherapy or immunotherapy would be non-inferior in progression-free survival (PFS) for this patient population when compared to the standard treatment.

The study enrolled 384 patients with p16+ oropharyngeal squamous cell carcinoma and ≤ 10 pack-years history of smoking.

Following stratification by Zubrod Performance Status, patients were randomly assigned to one of three potential treatment arms.

Treatment arm 1 was the control arm of 70 Gy of radiation in 6 weeks, 6 fractions per week with cisplatin every 3 weeks.

Treatment arm 2 included a lower dose of radiation at 60 Gy over 6 weeks in 5 fractions per week with cisplatin.

Treatment arm 3 was the lower dose of 60 Gy of radiation in 5 weeks and 6 fractions per week with nivolumab starting 1 week before radiation and given every 2 weeks.

The futility analysis for Treatments 1 and 2 was conducted at 11 PFS events which occurred with a median follow-up of 1.1 years and crossed the futility boundary.

The futility analysis for Treatments 1 and 3 was triggered after 11 PFS events after the phase II portion of the trial had already completed accrual and it also crossed the futility boundary.

At the present median follow up of 2.2 years, 2-year PFS estimates are 98.1% (95% CI 95.4, 100) for the control arm, 88.6% (95% CI 82.4, 94.7) for the lower dose radiation and cisplatin arm, and 90.3% (95% CI 84.5, 96.1) for the lower dose radiation and nivolumab arm.

The very high 98% PFS rate at 2 years of the control arm is part of the reason for the failure of the experimental arms to satisfy non-inferiority.

This study was sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and was supported by grants UG1CA189867 (NCORP), U10CA180822 (NRG Oncology SDMC), U10CA180868 (NRG Oncology Operations), U24CA180803 (IROC) from the NCI and Bristol Myers Squibb under a Cooperative Research and Development Agreement between NCI and BMS.

Source: NRG Oncology