Phase II Study of Roniciclib in Combination with Cisplatin/Etoposide or Carboplatin/Etoposide as First-Line Therapy in Patients with Extensive-Disease Small Cell Lung Cancer
Martin Reck, Leora Horn, Silvia Novello, Fabrice Barlesi, István Albert, Erzsébet Juhász, Dariusz Kowalski, Gilles Robinet, Jacques Cadranel, Paolo Bidoli, John Chung, Arno Fritsch, Uta Drews, Andrea Wagner, Ramaswamy Govindan, Martin Reck, Leora Horn, Silvia Novello, Fabrice Barlesi, István Albert, Erzsébet Juhász, Dariusz Kowalski, Gilles Robinet, Jacques Cadranel, Paolo Bidoli, John Chung, Arno Fritsch, Uta Drews, Andrea Wagner, Ramaswamy Govindan
Abstract
Introduction: This phase II study evaluated the efficacy and safety of the pan-cyclin-dependent kinase inhibitor roniciclib with platinum-based chemotherapy in patients with extensive-disease SCLC.
Methods: In this randomized, double-blind study, unselected patients with previously untreated extensive-disease SCLC received roniciclib, 5 mg, or placebo twice daily according to a 3 days-on, 4 days-off schedule in 21-day cycles, with concomitant cisplatin or carboplatin on day 1 and etoposide on days 1 to 3. The primary end point was progression-free survival. Other end points included overall survival, objective response rate, and safety.
Results: A total of 140 patients received treatment: 70 with roniciclib plus chemotherapy and 70 with placebo plus chemotherapy. Median progression-free survival times was 4.9 months (95% confidence interval [CI]: 4.2-5.5) with roniciclib plus chemotherapy and 5.5 months (95% CI: 4.6-5.6) with placebo plus chemotherapy (hazard ratio [HR] = 1.242, 95% CI: 0.820-1.881, p = 0.8653). Median overall survival times was 9.7 months (95% CI: 7.9-11.1) with roniciclib plus chemotherapy and 10.3 months (95% CI: 8.7-11.9) with placebo plus chemotherapy (HR = 1.281, 95% CI: 0.776-1.912, p = 0.7858). The objective response rates were 60.6% with roniciclib plus chemotherapy and 74.6% with placebo plus chemotherapy. Common treatment-emergent adverse events in both groups included nausea, vomiting, and fatigue. Serious treatment-emergent adverse events were more common with roniciclib plus chemotherapy (57.1%) than with placebo plus chemotherapy (38.6%).
Conclusions: Roniciclib combined with chemotherapy demonstrated an unfavorable risk-benefit profile in patients with extensive-disease SCLC, and the study was prematurely terminated.
Trial registration: ClinicalTrials.gov NCT02161419.
Keywords: CDK inhibitor; Carboplatin; Cisplatin; Etoposide; Extensive-disease small cell lung cancer; Roniciclib.
Copyright © 2019. Published by Elsevier Inc.
Source: PubMed