학술논문
NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma
Document Type
article
Author
Cecchini, Michael; Cleary, James M; Shyr, Yu; Chao, Joseph; Uboha, Nataliya; Cho, May; Shields, Anthony; Pant, Shubham; Goff, Laura; Spencer, Kristen; Kim, Edward; Stein, Stacey; Kortmansky, Jeremy S; Canosa, Sandra; Sklar, Jeffrey; Swisher, Elizabeth M; Radke, Marc; Ivy, Percy; Boerner, Scott; Durecki, Diane E; Hsu, Chih-Yuan; LoRusso, Patricia; Lacy, Jill
Source
British Journal of Cancer. 130(3)
Subject
Language
Abstract
BackgroundOur preclinical work revealed tumour hypoxia induces homologous recombination deficiency (HRD), increasing sensitivity to Poly (ADP-ribose) polymerase inhibitors. We aimed to induce tumour hypoxia with ramucirumab thereby sensitising tumours to olaparib.Patients and methodsThis multi-institution single-arm Phase 1/2 trial enrolled patients with metastatic gastroesophageal adenocarcinoma refractory to ≥1 systemic treatment. In dose escalation, olaparib was evaluated at escalating dose levels with ramucirumab 8 mg/kg day 1 in 14-day cycles. The primary endpoint of Phase 1 was the recommended Phase 2 dose (RP2D), and in Phase 2 the primary endpoint was the overall response rate (ORR).ResultsFifty-one patients received ramucirumab and olaparib. The RP2D was olaparib 300 mg twice daily with ramucirumab 8 mg/kg. In evaluable patients at the RP2D the ORR was 6/43 (14%) (95% CI 4.7-25.6). The median progression-free survival (PFS) was 2.8 months (95% CI 2.3-4.2) and median overall survival (OS) was 7.3 months (95% CI 5.7-13.0). Non-statistically significant improvements in PFS and OS were observed for patients with tumours with mutations in HRD genes.ConclusionsOlaparib and ramucirumab is well-tolerated with efficacy that exceeds historical controls with ramucirumab single agent for gastric cancer in a heavily pre-treated patient population.