SELECT-2: a phase II,double-blind,randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer |
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| Affiliation: | 1. Department of Medical Oncology, Gustave Roussy, Villejuif, France;;2. Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf (M.R.), Germany;;3. Department of Electrical Engineering, University of São Paulo, São Carlos, São Paulo, Brazil;;4. Department of Internal Medicine II, Lungenklinik Löwenstein GmbH, Löwenstein, Germany;;5. Department of Medical Oncology, Centro Integrado de Pesquisa, Fundação Faculdade Regional de Medicina de São José do Rio Preto, São José do Rio Preto;;6. Department of Oncology, Serviço de Oncologia do Hospital São Lucas da PUCRS, Porto Alegre, Brazil;;7. Department of Thoracic Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands;;8. Department of Tumor Biology, National Koranyi Institute of Pulmonology, Budapest, Hungary;;9. Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Ruhrlandklinik, University Duisburg-Essen, Essen, Germany;;10. Department of Medical Oncology, Individualna Praktika Za Spetsializirana Meditsinska Pomosht, Vratsa, Bulgaria;;11. AstraZeneca, Macclesfield, UK;;12. AstraZeneca, Cambridge, UK;;13. Novartis, Uxbridge, UK;;14. Lowe Center for Thoracic Oncology and The Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, USA |
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| Abstract: | BackgroundCombination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC.Patients and methodsPatients who had disease progression after first-line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.i.d. plus docetaxel 60 or 75 mg/m2 (SEL + DOC 60; SEL + DOC 75), or placebo plus docetaxel 75 mg/m2 (PBO + DOC 75). Patients were initially enrolled independently of KRAS mutation status, but the protocol was amended to include only patients with centrally confirmed KRAS wild-type NSCLC. Primary end point was progression-free survival (PFS; RECIST 1.1); statistical analyses compared each selumetinib group with PBO + DOC 75 for KRAS wild-type and overall (KRAS mutant or wild-type) populations.ResultsA total of 212 patients were randomized; 69% were KRAS wild-type. There were no statistically significant improvements in PFS or overall survival for overall or KRAS wild-type populations in either selumetinib group compared with PBO + DOC 75. Overall population median PFS for SEL + DOC 60, SEL + DOC 75 compared with PBO + DOC 75 was 3.0, 4.2, and 4.3 months, HRs: 1.12 (90% CI: 0.8, 1.61) and 0.92 (90% CI: 0.65, 1.31), respectively. In the overall population, a higher objective response rate (ORR; investigator assessed) was observed for SEL + DOC 75 (33%) compared with PBO + DOC 75 (14%); odds ratio: 3.26 (90% CI: 1.47, 7.95). Overall the tolerability profile of SEL + DOC was consistent with historical data, without new or unexpected safety concerns identified.ConclusionThe primary end point (PFS) was not met. The higher ORR with SEL + DOC 75 did not translate into prolonged PFS for the overall or KRAS wild-type patient populations. No clinical benefit was observed with SEL + DOC in KRAS wild-type patients compared with docetaxel alone. No unexpected safety concerns were reported.Trial identifierClinicaltrials.gov NCT01750281. |
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