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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

NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma

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  • Medientyp: E-Artikel
  • Titel: NCI10066: a Phase 1/2 study of olaparib in combination with ramucirumab in previously treated metastatic gastric and gastroesophageal junction adenocarcinoma
  • Beteiligte: 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
  • Erschienen: Springer Science and Business Media LLC, 2024
  • Erschienen in: British Journal of Cancer
  • Sprache: Englisch
  • DOI: 10.1038/s41416-023-02534-1
  • ISSN: 0007-0920; 1532-1827
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Our 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.</jats:p> </jats:sec><jats:sec> <jats:title>Patients and methods</jats:title> <jats:p>This 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).</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Fifty-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.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Olaparib 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.</jats:p> </jats:sec>