Nimorazole Provides No Benefit in Head and Neck Cancers With Tumor Hypoxia

Adding nimorazole to definitive radiotherapy does not improve outcomes in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) who have tumor hypoxia, results from the phase 3 NIMRAD trial suggest.

Nimorazole, a hypoxic cell radiosensitizer, did not improve loco-regional control or survival when added to intensity-modulated radiation therapy (IMRT), according to David Thomson MD, of the Christie NHS Foundation Trust in Manchester, United Kingdom. 

“The lack of effect was observed in those with more hypoxic tumors and for the whole population,” Dr Thomson said when presenting these findings at the ASCO Annual Meeting 2023. 

The phase 3 NIMRAD trial (ClinicalTrials.gov Identifier: NCT01950689) included 338 patients with HNSCC who had tumor hypoxia and were not suitable for concurrent platinum chemotherapy or monoclonal antibody therapy on the basis of fitness, comorbidity, or advanced age.

The patients were randomly assigned to receive nimorazole prior to IMRT (n=168) or IMRT alone (n=170). IMRT was given at 65 Gy in 30 fractions over 6 weeks. Nimorazole was given at 1.2 g/m² daily.

Baseline characteristics were well balanced between the arms. In the overall cohort, the median age was 73 years, 96% of patients had stage III/IV HNSCC, and 66% were HPV-positive. 

Hypoxia scores were available for 144 patients in the nimorazole arm and 142 patients in the IMRT-alone arm. The hypoxia-enriched group — who had hypoxia scores of 0.079 or higher — consisted of 70 patients in the nimorazole arm and 69 patients in the IMRT-alone arm. 

The study’s primary endpoint was freedom from loco-regional failure in the hypoxia-enriched group. There was no significant difference in this endpoint between the treatment arms in patients with more hypoxic tumors (hazard ratio [HR], 0.72; 95% CI, 0.36-1.44; P =.35) or in the overall cohort (HR, 0.76; 95% CI, 0.48-1.21; P =.25). 

There was no significant difference in disease-free survival between the treatment arms in patients with more hypoxic tumors (HR, 0.99; 95% CI, 0.60-1.64; P =.98) or in the overall cohort (HR, 1.00; 95% CI, 0.73-1.37; P =.98).

There was no significant difference in cancer-specific survival between the treatment arms in patients with more hypoxic tumors (HR, 0.89; 95% CI, 0.44-1.80; P =.75) or in the overall cohort (HR, 0.92; 95% CI, 0.60-1.42; P =.72).

There was no significant difference in overall survival between the treatment arms in patients with more hypoxic tumors (HR, 0.96; 95% CI, 0.53-1.72; P =.88) or in the overall cohort (HR, 0.92; 95% CI, 0.65-1.31; P =.66).

Nimorazole was moderately tolerated, according to Dr Thomson. Most patients in the nimorazole arm (73%) adhered to the drug for at least half of the IMRT fractions.

However, there was an increased risk of nausea in the nimorazole arm. The rate of grade 1-2 nausea was 56.5% in the nimorazole arm and 42.4% in the IMRT-alone arm. The rate of grade 3 nausea was 10.1% and 5.3%, respectively.

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

Reference

Thomson D, Slevin N, Baines H, et al. Randomised phase III trial of the hypoxia modifier nimorazole added to radiotherapy with benefit assessed in hypoxic head and neck cancers determined using a gene signature (NIMRAD). ASCO 2023. June 2-6, 2023. Abstract 6006.