In a prespecified interim analysis of a phase III trial (University of Texas MD Anderson Cancer Center Clinical Trial Consortium trial) reported in The Lancet, Frank et al found that intensity-modulated proton therapy (IMPT) was noninferior to standard intensity-modulated photon radiation therapy (IMRT) in progression-free survival among patients with stage III or IV oropharyngeal cancer.
Study Details
In the U.S. open-label noninferiority multicenter trial, 440 patients were randomly assigned between October 2013 and May 2022 to receive IMPT (n = 221) or IMRT (n = 219) with institutional tumor board choice of concurrent systemic therapy. All patients received radiotherapy to 70 Gy in 33 fractions to the primary tumor and cervical lymphadenopathy. The primary endpoint was progression-free survival in the intention-to-treat (ITT) population. The noninferiority margin for progression-free survival at 3 years was nine percentage points.
Key Findings
A total of 160 patients in the IMPT group (72%) received IMPT; a total of 136 patients in the IMRT group (62%) received IMRT.
Median follow-up was 3.14 years (interquartile range = 1.92–5.47 years). On ITT analysis, progression-free survival rates were 82.5% (95% confidence interval [CI] = 76.1%–87.3%) in the IMPT group vs 83.0% (95% CI = 76.7%–87.7%) in the IMRT group at 3 years (hazard ratio [HR] = 0.88, 95% CI = 0.57–1.35, P = .005 for noninferiority of IMPT). Progression-free survival at 5 years was 81.3% (95% CI = 74.5%–86.5%) vs 76.2% (95% CI = 68.0%–82.6%).
Overall survival at 5 years was 90.9% in the IMPT group vs 81.0% in the IMRT group (HR = 0.58, 95% CI = 0.34–0.99, P = .045).
Severe lymphopenia was more common in the IMRT group (89% vs 76%), as were dysphagia (49% vs 31%), xerostomia (45% vs 33%), and gastrostomy tube dependence (40.2% vs 26.8%). Treatment-related death occurred in three patients in the IMPT group vs six in the IMRT group.
The investigators concluded: “IMPT showed non-inferiority to IMRT for progression-free survival, improvement in overall survival, similar disease control, and reduced high-grade toxicity relative to IMRT. Treatment-related and post-progression deaths occurred more frequently with IMRT. IMPT is a new standard-of-care treatment option for patients with oropharyngeal cancer.”
Steven J. Frank, MD, of the Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, is the corresponding author for The Lancet article.
DISCLOSURE: The study was funded by the National Institutes of Health, Hitachi America, and others. For full disclosures of the study authors, visit thelancet.com.
