Martin Reck1, Leora Horn2, Silvia Novello3, Fabrice Barlesi4, István Albert5, Erzsébet Juhász6, Dariusz Kowalski7, Gilles Robinet8, Jacques Cadranel9, Paolo Bidoli10, John Chung11, Arno Fritsch12, Uta Drews13, Andrea Wagner13, Ramaswamy Govindan14. 1. LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany. Electronic address: dr.martin.reck@web.de. 2. Vanderbilt University Medical Center, Nashville, Tennessee. 3. Department of Oncology, University of Turin, Orbassano, Turin, Italy. 4. Aix-Marseille University, Marseille, France; Assistance Publique-Hôpitaux de Marseille, Marseille, France. 5. Pulmonary Department, Mátraháza Hospital, Mátraháza, Hungary. 6. Korányi National Institute for Pulmonology, Budapest, Hungary. 7. Maria Sklodowska-Curie Institute of Oncology, Warsaw, Poland. 8. University Hospital Brest, Brest, France. 9. Assistance Publique-Hôpitaux de Paris, Paris, France. 10. San Gerardo Hospital, Monza, Italy. 11. Bayer HealthCare Pharmaceuticals, Inc., Whippany, New Jersey. 12. Bayer AG, Wuppertal, Germany. 13. Bayer AG, Berlin, Germany. 14. Washington University School of Medicine, St. Louis, Missouri.
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 receivedroniciclib, 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 withroniciclib 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.
RCT Entities:
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.
Authors: Tiandong Kong; Lu Chen; Xiaoli Zhao; Fangfang Duan; Hanli Zhou; Lei Wang; Danna Liu Journal: Invest New Drugs Date: 2022-07-05 Impact factor: 3.651