Hypoxia-Guided Treatment Feasible in HPV-Related Oropharyngeal  Cancer

Hypoxia-guided chemoradiotherapy appears feasible for patients with HPV-related oropharyngeal cancer, according to research published in the Journal of Clinical Oncology.

Researchers found evidence to suggest that de-escalating chemoradiotherapy in patients with nonhypoxic tumors may reduce toxicity without compromising efficacy.

This phase 2 trial (ClinicalTrials.gov identifier: NCT03323463) included 152 patients with HPV-related oropharyngeal carcinoma who underwent primary tumor resection with intact gross nodal disease. Patients had a baseline ¹⁸F-fluoromisonidazole PET scan to measure tumor hypoxia, and these scans were repeated 1-2 weeks intratreatment.

There were 128 patients who had nonhypoxic tumors at baseline or later had resolution of hypoxia. They received de-escalated treatment consisting of 30 Gy of intensity-modulated radiation therapy (IMRT) plus 2 cycles of chemotherapy (cisplatin or carboplatin).

The remaining 24 patients had persistent hypoxic tumors. They received a total IMRT dose of 70 Gy plus 3 cycles of chemotherapy.

The study’s primary endpoint was a 2-year locoregional control rate of 95%. At a median follow-up of 38.3 months, the 2-year locoregional control rate in the full cohort was 94.7%, so the primary endpoint was met.

In the de-escalated treatment group, there were 8 patients who developed nodal recurrence at a median of 8.1 months. Persistent nodal disease was present in 4 of the patients. All 8 patients underwent successful neck dissections. There were no nodal recurrences in the standard treatment group.

One patient in the de-escalated treatment group developed distant metastasis, and 1 patient in the standard treatment group died of a pulmonary embolism.

The 2-year disease-specific survival rate was 100% in the overall cohort. The 2-year progression-free survival rate was 94% overall, 94% in the de-escalated group, and 96% in the standard group (P =.71). The 2-year overall survival rate was 99% overall, 100% in the de-escalated group, and 96% in the standard group (P =.021).

Patients in the standard treatment group experienced more acute grade 3-4 adverse events (AEs) than those in the de-escalated group. Acute grade 3-4 AEs related to IMRT included dysphagia (0.7%) in the de-escalated group and dysphagia (8.3%), dermatitis (4.2%), and oral mucositis (4.2%) in the standard group.

Acute grade 3-4 AEs related to chemotherapy (in the de-escalated and standard groups, respectively) included neutropenia (29.7% vs 45.8%), anemia (0.7% vs 4.2%), nausea (0.7% vs 4.2%), vomiting (1.5% vs 0%), and acute kidney injury (0.7% vs 4.2%).

There were no late grade 3-4 AEs related to IMRT in the de-escalated group, but 4.5% of patients in the standard group had grade 3-4 dysphagia. The only late grade 3-4 AE related to chemotherapy was anemia (0.7%), observed in the de-escalated group.

“Tumor hypoxia is a promising approach to direct dosing of curative-intent chemoradiotherapy for HPV-related carcinomas with preserved efficacy and substantially reduced toxicity that requires further investigation,” the researchers concluded. “A phase III trial is currently being planned to compare this precision radiotherapy approach with the current standard of care.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

This article originally appeared on Cancer Therapy Advisor