Abstract 3894
Background
Alisertib, a selective AAK inhibitor, showed single-agent antitumor activity in preclinical in vivo SCLC models and was synergistic with P in this setting. We report the efficacy (PFS, OS, ORR) and safety from this study.
Methods
Pts ≥18 y with SCLC relapsed
Results
178 pts were randomized (89/89) Arm A/B; median age 62/62 y. The analysis of PFS using IVRS stratification favored Arm A (median 101 vs 66 d) with HR 0.77; 95% CI 0.557, 1.067; p = 0.113. The analysis for PFS using the corrected stratification factors again favored Arm A with HR 0.72; 95% CI 0.522, 1.004; p = 0.038. Median OS was 186 vs 165 d, with HR 0.93; 95% CI 0.652, 1.341; p = 0.714 and ORR was 22% vs 18%, disease control rate 58% vs 46%, stable disease 55% vs 49%, and progressive disease 15% vs 26%. Pts received a median of 3 (1–9) vs 2 (1–11) cycles. Rates of AEs were higher in Arm A.
Safety population
| Arm A | (n = 87) | Arm B | (n = 89) |
|---|---|---|---|
| AE (≥20%) | % | AE (≥20%) | % |
| Diarrhea | 59 | Nausea | 34 |
| Neutropenia | 49 | Fatigue | 33 |
| Anemia | 44 | Constipation | 24 |
| Fatigue | 44 | Vomiting | 24 |
| Nausea | 33 | ↓ Appetite | 21 |
| Stomatitis | 33 | Dyspnea | 21 |
| ↓ Appetite | 33 | Anemia | 20 |
| Vomiting | 32 | Diarrhea | 20 |
| Dyspnea | 24 | ||
| Cough | 20 | ||
| Grade ≥3 AE | 76% | Grade ≥3 AE | 51% |
| Drug-related Grade ≥3 AEs | 67% | Drug-related Grade ≥3 AEs | 25% |
| Drug-related serious AEs | 32% | Drug-related serious AEs | 7% |
| AEs leading to treatment discontinuation | 15% | AEs leading to treatment discontinuation | 6% |
Conclusions
Alisertib + P shows favorable PFS over placebo + P with both corrected and IVRS stratification. A similar favorable trend was observed for OS and ORR. The alisertib + P arm showed higher rates of AEs and discontinuation due to AEs. Further analyses are pending.
Clinical trial identification
NCT02038647; EudraCT 2013-003713-18 (Clinical Trial Protocol C14018 Protocol Amend 2 2015-01-23)
Legal entity responsible for the study
Millennium Pharmaceuticals, Inc.
Funding
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
Disclosure
T.K. Owonikoko: Consulting: Medivation, Novartis, Lilly, Amgen; Research funding: Novartis, Stemcentrix, BMS, Celgene, AstraZeneca, Takeda, Regeneron, G1 Therapeutics, Calithera, AbbVie. E. Sheldon-Waniga, D. Huebner: Employment (Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited). E.J. Leonard: Employment (Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited); stock ownership: Takeda Pharmaceutical Company Limited; Corporate-sponsored research: Takeda-sponsored clinical trial. All other authors have declared no conflicts of interest.
Resources from the same session
Small cell lung carcinoma harbors targetable alterations including MYCL1 fusions responding to aurora kinase inhibitor
Presenter: Siraj Ali
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Abstract
Quality of resection and outcome in stage III thymic epithelial tumors (TET): A retrospective analysis of 150 cases from the national network RYTHMIC experience
Presenter: Maria Bluthgen
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Abstract
Phase II study of roniciclib in combination with cisplatin/etoposide or carboplatin/etoposide as first-line therapy in subjects with extensive-disease small cell lung cancer (ED-SCLC)
Presenter: Martin Reck
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Abstract
Patient-reported outcomes (PROs) and impact of lactate dehydrogenase (LDH) levels on outcomes in a phase 3 trial (NGR015) with best investigator choice (BIC) plus or minus NGR-hTNF in previously treated patients with malignant pleural mesothelioma (MPM)
Presenter: Vanesa Gregorc
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Abstract
Pathological central review of 400 thymic epithelial tumors (TET): The national network RYTHMIC experience
Presenter: Thierry Molina
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Abstract
Neoadjuvant anti-PD1, nivolumab, in early stage resectable non-small-cell lung cancer
Presenter: Patrick Forde
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Abstract
Presentation
Webcast
Multi-centre randomized controlled study comparing adjuvant vs neo-adjuvant chemotherapy with docetaxel plus carboplatin in resectable stage IB to IIIA NSCLC: final results of CSLC0501
Presenter: Yi-Long Wu
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Abstract
Presentation
Webcast
Low dose CT scan screening versus empiric surveillance in asbestos exposed subjects: Update of ATOM 002 study
Presenter: Gianpiero Fasola
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Abstract
Invited discussant LBA41 and abstract 1178O
Presenter: Paul Baas
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Presentation
Webcast
Invited discussant abstracts 1509PD and 1510PD
Presenter: Enrico Ruffini
Session: Non-metastatic NSCLC and other thoracic malignancies
Resources:
Presentation
Webcast