A randomized, phase 2 evaluation of the CHK1 inhibitor, LY2603618, administered in combination with pemetrexed and cisplatin in patients with advanced nonsquamous non‐small cell lung cancer

• Verfasst von: Wehler, Thomas Christian [VerfasserIn]
• Verfasst von: Thomas, Michael [VerfasserIn]
• Verfasst von: Schumann, Christian [VerfasserIn]
• Titel: A randomized, phase 2 evaluation of the CHK1 inhibitor, LY2603618, administered in combination with pemetrexed and cisplatin in patients with advanced nonsquamous non‐small cell lung cancer
• Verf.angabe: Thomas Wehler, Michael Thomas, Christian Schumann, Joaquim Bosch-Barrera, Nuria Viñolas Segarra, Nicolas J. Dickgreber, Klaus Dalhoff, Martin Sebastian, Jesus Corral Jaime, Miriam Alonso, Scott M. Hynes, Ji Lin, Karla Hurt, Aimee Bence Lin, Emiliano Calvo, Luis Paz-Ares
• E-Jahr: 2017
• Jahr: June 2017
• Umfang: 5 S.
• Fussnoten: Gesehen am 04.04.2019
• Titel Quelle: Enthalten in: Lung cancer
• Ort Quelle: Amsterdam [u.a.] : Elsevier, 1985
• Jahr Quelle: 2017
• Band/Heft Quelle: 108(2017), Seite 212-216
• ISSN Quelle: 1872-8332
• DOI: doi:10.1016/j.lungcan.2017.03.001
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Checkpoint kinase 1
• Sach-SW: Cisplatin
• Sach-SW: LY2603618
• Sach-SW: Non-small cell lung cancer
• Sach-SW: Pemetrexed
• K10plus-PPN: 1662814534

Abstract

This phase 2 portion of a phase 1/2 study examined the efficacy and safety of LY2603618, a selective checkpoint kinase 1 inhibitor, combined with pemetrexed and cisplatin (LY+Pem+Cis) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). This multicenter, randomized, controlled, open-label study (NCT01139775) enrolled patients with stage IV nonsquamous NSCLC and an Eastern Cooperative Oncology Group performance status ≤1. Patients were randomized (2:1) to LY+Pem+Cis or pemetrexed and cisplatin (Pem+Cis). Induction therapy comprised four 21-day cycles of 500 mg/m2 pemetrexed and 75mg/m2 cisplatin on Day 1 (both arms) and 275mg LY2603618 on Day 2 (LY+Pem+Cis arm). Maintenance therapy comprised 500mg/m2 pemetrexed on Day 1 (both arms) and 275mg LY2603618 on Day 2 (LY+Pem+Cis arm) until disease progression. The primary endpoint was progression‐free survival (PFS). Enrollment was permanently halted before target enrollment was met due to a greater number of thromboembolic events in the LY+Pem+Cis arm. Sixty-two patients were enrolled (LY+Pem+Cis, n=39; Pem+Cis, n=23). Bayesian and frequentist analysis demonstrated superior PFS in the LY+Pem+Cis arm vs the Pem+Cis arm (median [90% confidence interval]: LY+Pem+Cis, 4.7 months [4.-7.1]; Pem+Cis, 1.5 months [1.3-2.9]; P=0.022). Seven patients in the LY+Pem+Cis arm (vs 0 in the Pem+Cis arm) experienced serious thromboembolic events: pulmonary embolism (n=5), ischemic stroke (n=1), and cerebrovascular accident (n=1). Although the primary endpoint was met, the combination of LY2603618+Pem+Cis will not be further developed for treating advanced nonsquamous NSCLC due to the potential increased risk of thromboembolic events with this combination. ClinicalTrials.gov Identifier: NCT01139775.