Reduced-dose intensity-modulated radiation therapy (IMRT) plus cisplatin bested the 2-year progression-free survival (PFS) historical control rate in patients with good-risk human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), justifying the regimen’s advancement to a phase 3 study, according to results from the NRG-HN002 study published in the Journal of Clinical Oncology.
In the phase 2 study (NCT02254278), 306 patients with p16-positive OPSCC and a 10 year or fewer pack-year smoking history were randomly assigned to receive 60 Gy of IMRT over 6 weeks with concurrent weekly cisplatin or 60 Gy IMRT alone over a 5-week period. To proceed to a phase 3 evaluation, 1 arm had to achieve a 2-year PFS superior to the historical control rate of 85% and a 1-year mean composite score of 60 or more on the MD Anderson Dysphagia Inventory (MDADI).
The 2-year progression-free survival for IMRT plus cisplatin was 90.5%. For IMRT alone it was 87.6% (P =.23). There was also no significant difference seen in the 2-year overall survival rates between the 2 arms (96.7% and 97.3%, respectively).
The researchers noted that the survival in both arms was similar, but wrote that patterns of disease failure seen in the study were “instructive.”
“The IMRT patients, using a lower-than-standard dose in a radiotherapy-alone regimen, experienced a higher rate of locoregional failure, and two thirds of these patients were at the primary site,” they said. “In these radiation-only patients, there was a suggestion of increased locoregional in concert with tumor stage, suggesting the need for more treatment with increasing tumor burden.”
One-year MDADI mean scores were 85.30 for IMRT with cisplatin and 81.76 for IMRT alone.
There were higher rates of grade 3 or higher acute adverse events (AEs)—defined as AEs that occurred within 180 days from the end of treatment—reported in the cisplatin-containing arm (79.6% vs. 52.4%; P<.001). There was no significant difference in the rate of late grade 3 to 4 AEs between the 2 arms (21.3% vs 18.1; P =.56).
“Deintensification balances a reduction in high-grade toxicity against the opportunity for cure. Although both the arms in this study performed relatively well, there is high confidence that the CRT arm did not compromise PFS. The next step as determined within NRG Oncology is a randomized phase 2 and 3 trial,” the investigators concluded.
This ensuing trial (NCT03952585) is currently recruiting 711 patients with early-stage, HPV-positive, non-smoking associated OPSCC.
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
Yom SS, Torres-Saavedra P, Caudell JJ, et al. Reduced-dose radiation therapy for HPV-associated oropharyngeal carcinoma (NRG Oncology HN002). J Clin Oncol. Published online January 28, 2021. doi:10.1200/JCO.20.03128