Deintensification for Oropharyngeal Cancer Halted After Failing to Reach Standard of Care

Two strategies that were designed to deintensify radiation treatments for people with early-stage human papillomavirus (HPV)–associated oropharyngeal cancer have been stopped early after they failed to reach the standard of care, as reported by researchers at the American Society for Radiation Oncology (ASTRO) 2024 Annual Meeting and published in the International Journal of Radiation Oncology.^1,2

In this study, Sue S. Yom, MD, PhD, FASTRO, principal investigator of the trial and the Irwin Mark Jacobs and Joan Klein Jacobs Distinguished Professor in Head and Neck Cancer Radiation Oncology at the University of California, San Francisco, and her team tested 2 lower-intensity treatment regimens against a control arm of more standard chemoradiation for people with HPV-associated, locoregionally advanced oropharyngeal squamous cell carcinomas.¹ The researchers randomly assigned 382 patients to 1 of 3 treatment arms: usual radiation dosing (70 Gy total mildly accelerated over 6 weeks) combined with cisplatin chemotherapy; a reduced radiation dose (60 Gy total over 6 weeks) combined with cisplatin; and a reduced radiation dose (60 Gy total mildly accelerated over 5 weeks) combined with an immunotherapy drug, nivolumab, in place of chemotherapy.

With a median follow-up of 2.2 years, the 2-year progression-free survival estimates were 98.1% following treatment on the control arm, 88.6% after reduced radiation with chemotherapy, and 90.3% after reduced radiation with immunotherapy. The 2-year overall survival estimates were 99%, 98%, and 96.1%, respectively.

“In cancer treatment, 98% progression-free survival at two years is a number you just don’t see,” Yom said in a press release about the results. “It’s the highest that has ever been published in the literature for head and neck cancer, and in and of itself, it is strong evidence that modern chemoradiation therapy is highly effective for these patients.”¹

Yom added that although deintensification strategies for HPV-associated oropharyngeal cancers remains of very high interest, their team’s research “makes clear that these approaches should remain very experimental. Further work needs to be done to find ways that we can reduce side effects while maintaining these extremely high cure rates.”¹

The phase 2 trial was designed to trigger a futility analysis for each experimental arm after a predetermined number of patients experienced disease progression. These tests showed that neither deintensified treatment approach met the threshold for noninferiority compared to the standard treatment, however, and the trial was closed early.

This study was supported by funding from the National Cancer Institution and Bristol-Myers Squibb.

References

1. Existing standard chemoradiation superior to deintensification approaches for HPV-related oropharyngeal cancer. Press release. ASTRO. September 30, 2024. Accessed October 18, 2024. www.astro.org/news-and-publications/news-and-media-center/news-releases/2024/astro24yom
2. Yom SS, Harris J, Caudell JJ, et al. Interim futility results of NRG-HN005, a randomized, phase II/III non-inferiority trial for non-smoking p16+ oropharyngeal cancer patients. Int J Radiat Oncol Biol Phys. 2024;120(2):S2-S3.