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).
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.
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.
Addition of R to platinum-based first-line chemotherapy in ED-SCLC patients increased toxicity without improving efficacy.
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Legal entity responsible for the study
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.