Standard whole brain radiation therapy (WBRT) with supplemental oxygen (O2), with or without RSR13 (efaproxiral)in patients with brain metastases: Results of the randomized REACH (RT-009) study

Abstract

1534 Background: Brain metastases represent a common cause of morbidity and mortality among cancer pts. The effectiveness of WBRT as primary therapy for brain metastases is limited by tissue hypoxia, which has been shown to cause radioresistance in solid tumors. RSR13 (efaproxiral) is a novel radiation sensitizer that acts as an allosteric modifier of hemoglobin, facilitates O2 release and decreases tissue hypoxia. Methods: A randomized, open-label Phase 3 study was conducted comparing RSR13 and WBRT to WBRT alone in pts. with newly diagnosed brain metastases from various solid tumors. In the RSR13 arm (n=271), pts. received RSR13 (75–100 mg/kg/d, IV) plus O2 followed by WBRT (30 Gy, 3 Gy/d x 10 days). In the Control arm (n=267), pts. received WBRT plus O2. The primary endpoint was survival. Secondary endpoints were RR in the brain, TTP, cause of death and QoL. Results: A total of 538 pts. were enrolled over 29 months at 82 sites in 12 countries. In the overall study population (n=538), the RSR13 arm demonstrated a 17.6% improvement in median survival time (MST) over the Control arm (5.26 mo vs. 4.47 mo; p=0.17). The survival benefit for RSR13 was statistically significant in a Cox multiple regression model (Hazard Ratio 0.78 [95% CI 0.64, 0.94], p=0.010). Pts. with breast cancer or NSCLC (n=414) receiving RSR13 had a 32.4% increase in MST vs. Control (5.91 vs. 4.47 mo; p=0.12). In pts. with breast cancer (n=115) the MST almost doubled in those who received RSR13 vs. Control (8.67 vs. 4.57 mo; p=0.006). The percentage of breast cancer pts. with stable/improved KPS at 3 months was significantly higher in the RSR13 arm (35% vs 18%, p=0.001). Related SAEs that are part of the RSR13 safety profile occurred in 7% of pts. The most common RSR13-related SAE was hypoxemia (3.4 %), which is dose-dependent and effectively managed with increased supplemental O2. Conclusions: The addition of RSR13 to WBRT was well tolerated and led to a 22% reduction in the risk of death for all pts. A near doubling in MST and significant improvement in QoL were observed in pts. with brain metastases from breast cancer. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Allos Therapeutics, Inc. Allos Therapeutics Allos Therapeutics, Inc. Allos Therapeutics