1426PD - Phase II study of roniciclib in combination with cisplatin/etoposide or carboplatin/etoposide as first-line therapy in subjects with extensive-dise...

Date 10 October 2016
Event ESMO 2016 Congress
Session Non-metastatic NSCLC and other thoracic malignancies
Topics Anticancer agents
Clinical research
Small Cell Lung Cancer
Basic Scientific Principles
Therapy
Biological Therapy
Presenter Martin Reck
Citation Annals of Oncology (2016) 27 (6): 493-496. 10.1093/annonc/mdw389
Authors M. Reck1, L. Horn2, S. Novello3, F. Barlesi4, I. Albert5, E. Juhasz6, J. Chung7, A. Fritsch8, U. Drews9, M. Rutstein7, A. Wagner9, R. Govindan10
  • 1Thoracic Oncology, Lung Clinic Grosshansdorf, Airway Research Center North (ARCN), German Center for Lung Research (DZL), 22927 - Grosshansdorf/DE
  • 2Oncology, Vanderbilt Ingram Cancer Center, Nashville/US
  • 3Department Of Oncology, University of Turin, Orbassano/IT
  • 4Multidisciplinary Oncology And Therapeutic Innovations Department, Aix Marseille University - Assistance Publique Hôpitaux de Marseille, Marseille/FR
  • 5Oncology, Mátrai Gyógyintézet, Matrahaza/HU
  • 6Pulmonology, National Koranyi Institute of Pulmonology, Budapest/HU
  • 7Clinical Development, Bayer HealthCare Pharmaceuticals, Whippany/US
  • 8Clinical Statistics, Bayer AG, Wuppertal/DE
  • 9Clinical Development, Bayer AG, Berlin/DE
  • 10Medical Oncology, Washington University School of Medicine, 63110 - St. Louis/US

Abstract

Background

Patients with ED-SCLC have a poor prognosis. We conducted a phase II study to evaluate the efficacy and safety of roniciclib (R), an oral pan-cyclin-dependent kinase inhibitor, in combination with standard first-line platinum-based chemotherapy in subjects with ED-SCLC (NCT02161419).

Methods

Chemotherapy-naïve ED-SCLC patients were randomized 1:1 to receive 5 mg R or placebo (P) BID, 3d-on/4d-off, and standard chemotherapy (etoposide with either cisplatin or carboplatin) on a 21-day schedule for 6 cycles after which R/P was continued as monotherapy. Treatment continued until disease progression, death, or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary objectives included overall survival (OS), time to progression (TTP), and objective response rate (ORR) and safety.

Results

A total of 140 patients with ED-SCLC started treatment with R plus chemotherapy (R-Chemo) or P-Chemo (70 in each arm). Baseline characteristics were balanced between R-Chemo and P-Chemo: male patients 61 vs 62%, ECOG status (0/1) 35/65% vs 28/72%, median age 62 vs 63 years. Median number of cycles during combination treatment was 4 vs 6 (R-Chemo vs P-Chemo), and dose reductions/treatment discontinuations due to AEs were 44/23% vs 13/6%. No significant differences in favor of R-Chemo were seen in the efficacy endpoints (R-Chemo vs P-Chemo): median PFS 4.9 mo vs 5.5 mo [HR 1.242 (CI: 0.82, 1.88), p-value 0.865]; median OS 10.7 mo vs 10.7 mo [HR 1.430 (CI: 0.79, 2.61), p-value 0.869]; median TTP 5.4 mo vs 5.5 mo [HR 1.047 (CI: 0.67, 1.65), p-value 0.590]; and ORR 61% vs 75% [p-value0.968 ]. Incidence of notable adverse events (AEs) higher in the R-Chemo arm included vomiting, diarrhea, hypomagnesemia, thromboembolic events, sepsis and acute kidney injury. There were 9 fatal AEs in the R-Chemo arm compared to one in the P-Chemo arm, with 2 attributed to R (sepsis and bronchopulmonary hemorrhage). Study treatment was discontinued for all ongoing patients.

Conclusions

Addition of R to platinum-based first-line chemotherapy in ED-SCLC patients increased toxicity without improving efficacy.

Clinical trial identification

NCT02161419

Legal entity responsible for the study

Bayer AG

Funding

Bayer AG

Disclosure

M. Reck: Honoraria for lectures and consultancy: Hoffmann-La Roche, Lilly, BMS, AstraZeneca, MSD, AstraZeneca, Boehringer-Ingelheim, Celgene, Pfizer, Novartis. L. Horn: Consulting agreement (uncompensated) – Bayer. S. Novello: Speaker Bureau for Eli Lilly, AZ, Roche, BMS, MSD. J. Chung, M. Rutstein: Employee of Bayer HealthCare Pharmaceuticals Inc. A. Fritsch, U. Drews, A. Wagner: Employee of Bayer AG. All other authors have declared no conflicts of interest.