TOPLINE:
Deintensified chemoradiotherapy using 60 Gy radiotherapy with concurrent weekly cisplatin was associated with low 5-year locoregional recurrence (3.4%) and overall survival exceeding 90% in patients with favorable-risk HPV-associated oropharyngeal carcinoma, according to a single-arm cohort study. These findings should, however, be interpreted in the context of recent randomized phase 2 data, which showed 60 Gy regimens did not meet noninferiority criteria compared with a 70 Gy regimen.
METHODOLOGY:
- Deintensification for HPV-associated oropharyngeal carcinoma is being explored in several ways, including by reducing radiation dose or providing less-toxic systemic therapy. A recent randomized controlled phase 2 trial found that the 60 Gy experimental arms failed noninferiority.
- In the current analysis, researchers evaluated a deintensified approach in more favorable-risk patients. A total of 240 patients with p16-positive oropharyngeal carcinoma (clinical stage T0-T3, N0-N2c) and a favorable smoking history received deintensified radiotherapy, with most also receiving concurrent chemotherapy, at several US institutions between September 2014 and August 2022.
- Treatment consisted of 60 Gy intensity-modulated radiotherapy delivered at 2 Gy per fraction once daily for 6 weeks, with concurrent chemotherapy prescribed for 205 patients (85.4%), including cisplatin 30 mg/m² weekly in 165 patients (68.8%) and cisplatin 40 mg/m² weekly in 20 patients (8.3%).
- Patients with clinical stage T0-T2 and N0-N1 disease were recommended to receive 60 Gy radiotherapy alone without chemotherapy, and 33 of 42 of these patients (78.6%) received radiotherapy alone.
- The primary outcome was locoregional recurrence; distant recurrence, progression-free survival (PFS), and overall survival were secondary outcomes. Median follow-up was 6.5 years.
TAKEAWAY:
- The 2-year locoregional recurrence rate was 1.3% and the 5-year rate was 3.4%.
- The 2-year overall survival was 97.9%, PFS was 94.1%, and distant recurrence was 4.6%. At 5 years, overall survival was 92.4%, PFS was 86.5%, and distant recurrence was 7.3%.
- Among 26 patients with recurrences, median time to progression was 1.9 years, with 12 (46.2%) occurring after 2 years.
- Multivariate analysis showed that patients with low-risk disease (T0-T2, N0-N1) treated with radiotherapy alone achieved 5-year PFS of 93.8% with no locoregional recurrences observed in this subgroup. Only higher nodal stage (N2b-N2c vs N0-N2a) was associated with worse PFS (adjusted hazard ratio, 2.58).
IN PRACTICE:
“Our single-arm institutional results do not alter the standard of care; however, they do provide evidence to support ongoing investigations of deintensified radiotherapy in patients with HPV-associated [oropharyngeal carcinoma],” the researchers concluded.
SOURCE:
The study, led by Ryan T. Morse, MD, Department of Radiation Oncology, University of Kansas Medical Center in Kansas City, was published online April 23 in JAMA Otolaryngology – Head & Neck Surgery.
LIMITATIONS:
A comparison to standard 7-week chemoradiotherapy could not be made in this single-arm analysis, limiting the ability to directly assess the relative benefits of deintensification. Long-term toxic effects and quality of life measures were not comprehensively reported, which would have enhanced understanding of the modestly reduced deintensified chemoradiotherapy regimen in this traditionally healthier population with HPV-associated oropharyngeal carcinoma, although initial toxic effect data were previously reported.
DISCLOSURES:
This work was partly supported by the National Cancer Institute through a University of North Carolina Lineberger Comprehensive Cancer Center Core Grant (P30-CA016086). Ryan T. Morse, MD, disclosed receiving a T32 geriatric oncology training grant from the National Institutes of Health (NIH) during the conduct of the study. Jared Weiss, MD, disclosed receiving personal fees from AstraZeneca, PDS Biotechnology, Amgen, Pharmacosmos, GSK, and Verastem, and grants from Eli Lilly, PDS Biotechnology, Genmab, Iovance, Nurix, TScan, Inspirna, Janux, Pharmacosmos, Bristol Myers Squibb, Summit Therapeutics, US Department of Defense, and NIH outside the submitted work. Additional 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.
