Multicenter phase 1-2 study of olaparib plus ramucirumab for previously treated metastatic gastric and gastroesophageal junction adenocarcinoma

Preclinical experiments showed that tumor hypoxia induces homologous recombination deficiency, increasing sensitivity to PARP inhibition. A multicenter phase 1-2 trial in the United States evaluated to combination of ramucirumab (inducing tumor hypoxia) plus olaparib (PARP inhibitor) fro previously treated metastatic gastric or gastroesophageal adenocarcinoma. The recommended phase 2 dose was olaparib 300 mg twice daily plus ramucirumab mg/kg every 14 days. The objective response rate with this combination was 14% (95% CI 4,7-25.6), while the median progression-free and overall survival were 2.8 months (2.3-4.2) and 7.3 months (5.7-13.0), respectively. The authors conclude that among patients with previously treated mG/GEJ adenocarcinoma, the combination of olaparib and ramucirumab was well-tolerated with efficacy that exceeded historical controls with ramucirumab as single agent.