In a study reported in the Journal of the National Cancer Institute, Beaty et al found that the presence of a PIK3CA mutation was associated with poorer disease-free survival among patients receiving deintensified definitive chemoradiotherapy for human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma. As noted by the investigators, PIK3CA is the most frequently mutated gene in HPV-associated oropharyngeal squamous cell carcinoma.
The prospective cohort included 77 patients with newly diagnosed HPV-associated oropharyngeal squamous cell carcinoma from two phase II trials performed at the University of North Carolina and University of Florida, respectively. Patients received deintensified chemoradiotherapy consisting of 60-Gy intensity-modulated radiotherapy with concurrent weekly cisplatin at 30 mg/m2. Targeted next-generation sequencing was performed to identify potentially deleterious mutations.
KEY POINTS
- Compared with patients with PIK3CA mutations, those with wild-type PIK3CA had significantly better 3-year disease-free survival (93.4% vs 68.8%).
- On multivariate analysis, PIK3CA mutation was the only variable independently associated with risk of disease recurrence.
Key Findings
Median follow-up was 24 months. Of 77 patients, 9 (12%) had disease recurrence, consisting of regional, distant, and regional and distant recurrence in 2, 4, and 3 patients, respectively. Mutations were identified in 34 patients (44%); PIK3CA mutations were the most common, being identified in 16 (21%).
Compared with patients with PIK3CA mutations, those with wild-type PIK3CA had significantly better 3-year disease-free survival (93.4% vs 68.8%, P = .004). On multivariate analysis, PIK3CA mutation was the only variable independently associated with risk of disease recurrence (hazard ratio = 5.71, P = .01).
The investigators concluded, “PIK3CA mutation is associated with worse disease-free survival in a prospective cohort of [patients with] newly diagnosed HPV-associated oropharyngeal squamous cell carcinoma treated with deintensified chemoradiotherapy…. [P]atients with PIK3CA mutations may not be suitable for deintensified therapy, and investigation of novel treatment strategies, such as with integration of immune checkpoint blockade therapy, may be appropriate.”
Bhishamjit Chera, MD, of the Department of Radiation Oncology, University of North Carolina School of Medicine, is the corresponding author for the Journal of the National Cancer Institute article.
Disclosure: The study was supported by the Department of Radiation Oncology, University of North Carolina Hospitals, and Lineberger Comprehensive Cancer Center, Chapel Hill. For full disclosures of the study authors, visit academic.oup.com.
