Trial results for the de-intensified radiation therapy study (NCT03952585) investigating nivolumab or cisplatin with reduced radiation for early-stage HPV-positive oropharyngeal cancer were posted on ClinicalTrials.gov on 2025-05-02. The study's Phase II analysis indicated that reduced radiation arms, including the nivolumab arm, did not meet the pre-specified non-inferiority criteria for progression-free survival compared to standard therapy.

Background

The study NCT03952585, titled "De-intensified Radiation Therapy With Chemotherapy (Cisplatin) or Immunotherapy (Nivolumab) in Treating Patients With Early-Stage, HPV-Positive, Non-Smoking Associated Oropharyngeal Cancer," is a Phase II/III trial. It aims to investigate how well a reduced dose of radiation therapy works with nivolumab compared to cisplatin in treating patients with human papillomavirus (HPV)-positive oropharyngeal cancer that is early in its growth and not associated with smoking.

Trial design

The Phase II/III trial NCT03952585 enrolled 384 participants and is currently ACTIVE_NOT_RECRUITING. It focuses on patients with early-stage, HPV-mediated oropharyngeal carcinoma, including Basaloid Squamous Cell Carcinoma, Clinical Stage I HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Clinical Stage II HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8, Oropharyngeal Squamous Cell Carcinoma, and Papillary Squamous Cell Carcinoma. Participants were assigned to one of three treatment arms:

The Phase II primary objective included assessing Progression-free Survival (PFS). The non-inferiority hypothesis for Phase II stipulated that the 90% upper confidence interval of the hazard ratio (experimental arm / standard arm) must be less than 2.4 for non-inferiority.

Key results

The trial's Phase II analysis included several key measurements. For Progression-free Survival (PFS), measured as the percentage of participants alive without progression, initial reported values were 99.1% for Arm I (Standard RT + Cisplatin), 96.4% for Arm II (Reduced RT + Cisplatin), and 96.6% for Arm III (Reduced RT + Nivolumab). Later measurements for PFS showed 98.1% for Arm I, 88.6% for Arm II, and 90.3% for Arm III.

For Locoregional Failure, measured as the percentage of participants with locoregional failure, initial reported values were 0.0% for Arm I, 2.7% for Arm II, and 1.7% for Arm III. Later measurements for locoregional failure showed 0.0% for Arm I, 6.5% for Arm II, and 5.0% for Arm III.

Key analyses for Progression-free Survival (PFS) hazard ratios (HR) comparing experimental arms to the standard arm in Phase II showed:

The pre-specified non-inferiority threshold for Phase II required the 90% upper confidence interval of the HR to be less than 2.4. Since both 19.46 and 14.85 exceeded this threshold, the null hypothesis for non-inferiority was not rejected for either reduced radiation arm.

Additional hazard ratios for Locoregional Failure were reported:

What this means

The Phase II results from this study indicate that the de-intensified radiation therapy regimens, whether combined with cisplatin or nivolumab, did not demonstrate non-inferiority in terms of progression-free survival compared to the standard radiation and cisplatin regimen. The observed hazard ratios for PFS, with upper confidence intervals significantly exceeding the pre-specified threshold of 2.4, suggest that these reduced-dose approaches may be associated with less favorable outcomes for patients with early-stage, HPV-positive oropharyngeal cancer. These findings are critical for guiding future treatment strategies in this patient population.

Source

The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT03952585, titled "De-intensified Radiation Therapy With Chemotherapy (Cisplatin) or Immunotherapy (Nivolumab) in Treating Patients With Early-Stage, HPV-Positive, Non-Smoking Associated Oropharyngeal Cancer," were posted on 2025-05-02 on clinicaltrials.gov.