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

Jean Charles Soria, A. Fülöp, C. Maciel, J. R. Fischer, G. Girotto, S. Lago, E. Smit, G. Ostoros, W. E.E. Eberhardt, P. Lishkovska, S. Lovick, G. Mariani, A. McKeown, E. Kilgour, P. Smith, K. Bowen, A. Kohlmann, D. J. Carlile, P. A. Jänne

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Abstract

Background: Combination 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 methods: Patients 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. Results: A 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. Conclusion: The 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.

Original languageEnglish
Pages (from-to)3028-3036
Number of pages9
JournalAnnals of Oncology
Volume28
Issue number12
DOIs
Publication statusPublished - Dec 1 2017

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Keywords

  • Advanced non-small-cell lung cancer (NSCLC)
  • Docetaxel
  • KRAS
  • MEK1/2
  • Metastatic disease
  • Selumetinib

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Soria, J. C., Fülöp, A., Maciel, C., Fischer, J. R., Girotto, G., Lago, S., Smit, E., Ostoros, G., Eberhardt, W. E. E., Lishkovska, P., Lovick, S., Mariani, G., McKeown, A., Kilgour, E., Smith, P., Bowen, K., Kohlmann, A., Carlile, D. J., & Jänne, P. A. (2017). 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. Annals of Oncology, 28(12), 3028-3036. https://doi.org/10.1093/annonc/mdx628