TOPLINE:

In a phase 3 trial of patients with stage III or IV oropharyngeal cancer, intensity-modulated proton therapy (IMPT) resulted in noninferior progression-free survival and better overall survival than intensity-modulated photon radiation therapy (IMRT), with fewer toxicities.

METHODOLOGY:

• Radiotherapy is an integral part of treating oropharyngeal cancer, but the current standard photon therapy, IMRT, can have significant toxicities. Proton therapy is a potentially safer alternative, but published trial data directly comparing the two approaches are lacking.
• Researchers conducted a randomized, open-label, noninferiority phase 3 trial enrolling 440 patients with stage III or IV oropharyngeal cancer (median age, 61 years) at 21 US centers between October 2013 and May 2022.
• Patients were randomly assigned to receive either IMPT (n = 221) or IMRT (n = 219). Treatment consisted of radiotherapy delivered at 70 Gy in 33 fractions to the primary tumor site and cervical lymphadenopathy, with induction or concurrent systemic therapy chosen by each institution’s tumor board.
• The primary endpoint was progression-free survival with a noninferiority margin of 9 percentage points at 3 years. Overall survival was a secondary endpoint. Safety outcomes were assessed in the per-protocol population (patients who received the assigned treatment).

TAKEAWAY:

• Progression-free survival rates with IMPT vs IMRT were 82.5% vs 83% at 3 years and 81.3% vs 76.2% at 5 years, demonstrating noninferiority of IMPT (hazard ratio [HR], 0.88; 95% CI, 0.57-1.35; P = .005).
• Overall survival at 5 years was 90.9% vs 81% for IMPT vs IMRT, favoring proton therapy (HR, 0.58; P = .045).
• Rates of severe toxicities were lower with IMPT than with IMRT, including lower rates of grade 3 or 4 lymphopenia (76% vs 89%), dysphagia (34% vs 49%), xerostomia (33% vs 45%), and gastrostomy tube dependence (26.8% vs 40.2%; P = .018).
• Treatment-related deaths occurred less frequently with IMPT than with IMRT (3 vs 6), and deaths from disease progression were also less frequent in the IMPT group than in the IMRT group (9 vs 18).

IN PRACTICE:

“To our knowledge, this is the first phase 3 trial in oropharyngeal cancer suggesting an improvement in overall survival from proton versus photon radiation therapy,” the authors of the study wrote. While data from other ongoing trials are still needed, they concluded, “This evidence shows that IMPT is a new standard-of-care treatment option for the management of oropharyngeal tumors.”

SOURCE:

The study, led by Steven J. Frank, MD, The University of Texas MD Anderson Cancer Center, Houston, was published online in The Lancet.

LIMITATIONS:

Delivery techniques for IMPT and IMRT were optimized throughout the trial period, with radiation delivery systems varying among participating institutions. Systemic therapy regimens were not uniform across sites. The study population (93% White) potentially limits the generalizability of the results across different demographic groups.

DISCLOSURES:

The study was funded by the MD Anderson Cancer Center, Massachusetts General Hospital, the National Institutes of Health, and Hitachi America. Two authors reported receiving grant support from Hitachi. Several authors reported receiving honoraria, consulting fees, and travel support from or having other ties with various sources. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.