1914MO Randomized phase II study of radiation therapy and paclitaxel with pazopanib or placebo: NRG-RTOG 0912

Abstract

Anaplastic thyroid cancer (ATC) is a rare/aggressive cancer with no standard radiation-based local treatment. Achieving locoregional disease control in the neck is critical due to major concerns of airway and esophageal compromise. Based on data suggesting synergy between pazopanib (P) and paclitaxel (T) in ATC, NRG Oncology conducted a randomized phase II study comparing concurrent T and intensity modulated radiation therapy (IMRT) with either P or placebo (C). The study arm evaluated 2-3 weeks of weekly T (80 mg/m2) and daily P suspension (PS) 400 mg followed by concurrent weekly T (50 mg/m2), daily PS (300 mg), and IMRT 66 Gy. The standard arm substituted C for PS. Inclusion criteria included pathologic diagnosis of M0/M1 ATC (central path review), Zubrod 0-2, no recent hemoptysis/bleeding, no brain metastases. Target accrual was 88 patients (pts) (79 eligible) to show a >37.5% reduction in the hazard rate for overall survival (OS) with addition of PS (1-sided alpha 0.15, beta 0.2). Final analysis, after accounting for 1 interim analysis, was 1-sided log-rank test at 0.1379 level in eligible pts. 89 pts (71 eligible) were accrued from 6/23/14-12/30/16, completing accrual 14 months earlier than projected. Pts excluded per protocol in each arm - PS 6; C 12. Median age 65 years. Female 52.1%. Zubrod 0-1 91.5%. Total thyroidectomy 36.6%; partial thyroidectomy 21.1%. M0 disease 56.3%. OS was not significantly higher with PS compared to C (p=0.28); hazard ratio (PS/C) was 0.86 (95% CI 0.52 - 1.43). OS and adverse events (AE) rates are in the table.Table: 1914MOPazopanib (n=36)Placebo (n=35)OS rate (95% CI)1-year37.1% (21.1-53.2%)29.0% (13.2-44.8%)2-year20.0% (6.7-33.3%)12.9% (1.1-24.6%)3-year17.1% (4.7-29.6%)9.7% (0-20.0%)Highest treatment-related AE(n=36)(n=34)Grade 352.8%55.9%Grade 433.3%26.5%Grade 52.8% (1 pt)2.9% (1 pt) Open table in a new tab NRG-RTOG 0912 is the largest randomized ATC study that completed accrual demonstrating feasibility in the cooperative group setting. Although a statistically significant improvement in OS was not seen with PS added to T and IMRT, the OS rates and feasibility data from this prospective clinical trial will be useful to help design future studies in this rare and aggressive disease.