Abstract C71: Phase II study of maintenance therapy with pazopanib or pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) who have not progressed following platinum-based chemotherapy.

Abstract

Abstract Background: Platinum-based chemotherapy combinations are the standard of care in first-line treatment of advanced NSCLC. Maintenance therapy with a chemotherapeutic agent (continuation maintenance) or a targeted agent (switch maintenance) has been explored to delay recurrence. The purpose of this trial (NCT01313663) was to evaluate the clinical activity and safety profile of pazopanib as switch maintenance in patients with stable disease or better as best response after induction therapy in advanced NSCLC. Methods: Eligible patients had received 4-6 cycles of induction therapy with cisplatin/carboplatin plus pemetrexed and should have had best response of complete response, partial response, or stable disease before entering the study. In this 2-arm, open-label, phase II study, patients were randomized to receive either oral pazopanib 800 mg daily or intravenous pemetrexed 500 mg/m2 on Day 1 of a 21-day cycle. The primary endpoint was to estimate the hazard ratio (HR) for investigator-assessed progression-free survival; secondary endpoints included overall survival, best overall response, and safety. Results: Planned enrollment was 200 patients. The trial was terminated due to evolving standards of care that resulted in a slow enrollment rate. Twenty patients were randomized and 19 received treatment (10 received pazopanib; 9 received pemetrexed). Progression-free survival was 10.3 weeks in the pemetrexed arm and 12.7 weeks in the pazopanib arm (HR = 0.92; 90% confidence interval: 0.32, 2.65). However, the number of evaluable patients was too small to draw conclusions for efficacy, as evidenced by the width of the 90% confidence interval for the HR. Best response was stable disease (2 patients in each arm). All patients experienced at least 1 adverse event (AE). Hepatic toxicities were more common with pazopanib, but low enrollment prevented a complete characterization of AE frequency. There were no fatal serious adverse events (SAEs) in the pazopanib arm and there were 2 fatal SAEs in the pemetrexed arm (respiratory failure and pneumonia). Conclusions: Low accrual and early termination prevented evaluation of the primary endpoint. No new safety signals emerged. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C71. Citation Format: Kartik Konduri, David Smith, Natalie Compton, Denise Elmore Lockheed, Debasis Chakrabarti, Kamal Bhatt. Phase II study of maintenance therapy with pazopanib or pemetrexed in patients with advanced non-small cell lung cancer (NSCLC) who have not progressed following platinum-based chemotherapy. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C71.