In a phase II trial (NRG/RTOG 0912) reported in The Lancet Oncology, Sherman et al found that the addition of pazopanib to concurrent radiotherapy and paclitaxel did not improve overall survival in patients with anaplastic thyroid cancer.

Study Details

In the U.S. multicenter, double-blind trial, 71 patients with anaplastic thyroid cancer (any TMN stage) were randomly assigned between June 2014 and December 2016 to receive pazopanib (n = 36) or placebo (n = 35) with concurrent paclitaxel and intensity-modulated radiotherapy (IMRT). Treatment consisted of 2 to 3 weeks of weekly paclitaxel at 80 mg/m² and daily pazopanib suspension at 400 mg orally or placebo followed by concurrent weekly paclitaxel at 50 mg/m², daily pazopanib at 300 mg, or placebo and IMRT at 66 Gy in 33 daily fractions.

The primary endpoint was overall survival in the intent-to-treat population.

Overall Survival

At final analysis (data cutoff in March 2020), median follow-up was 2.9 years (interquartile range = 0.002–4.0 years). Median overall survival was 5.7 months (95% confidence interval [CI] = 4.0–12.8 months) in the pazopanib group vs 7.3 months (95% CI = 4.3–10.6 months) in the control group (hazard ratio [HR] = 0.86, 95% CI = 0.52–1.43, P = .28). Overall survival at 1 year was 37.1% (95% CI = 21.1%–53.2%) in the pazopanib group vs 29.0% (95% CI = 13.2%–44.8%) in the control group (P = .24). In a post hoc analysis, hazard ratios were 1.21 (95% CI = 0.58–2.52) among patients with M1 (n = 26) or MX (n = 5) disease and 0.65 (95% CI = 0.32–1.31) in patients with M0 disease (n = 30; P = .23 for treatment-by–M stage interaction).   

Adverse Events

Grade ≥ 3 adverse events occurred in 88.9% of 36 patients in the pazopanib group and 85.3% of 34 in the control group who received study treatment (P = .73). The most common events included dysphagia (36% vs 29%), radiation dermatitis (22% vs 38%), increased alanine aminotransferase (33% vs 0%), increased aspartate aminotransferase (22% vs 0%), and oral mucositis (14% vs 24%).

Treatment-related serious adverse events occurred in 44% of patients (most commonly, dehydration and thromboembolic events, in 8% each) vs 35% of patients (most commonly, oral mucositis, in 8%). Treatment-related death occurred in one patient in the pazopanib group, due to sepsis, and one patient in the control group, due to pneumonitis.

Eric J. Sherman, MD

The investigators concluded, “To our knowledge, this study is the largest randomized anaplastic thyroid cancer study that has completed accrual showing feasibility in a multicenter National Cancer Institute National Clinical Trials Network setting. Although no significant improvement in overall survival was recorded in the pazopanib group, the treatment combination was shown to be feasible and safe, and hypothesis-generating data that might warrant further investigation were generated.”

Eric J. Sherman, MD, of the Division of Head and Neck Oncology, Memorial Sloan Kettering Cancer Center, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the National Cancer Institute and Novartis. For full disclosures of the study authors, visit ascopubs.org.