Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2017 Dec 1;28(12):3028-3036.
doi: 10.1093/annonc/mdx628.

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

J-C Soria  1 , A Fülöp  2 , C Maciel  3 , J R Fischer  4 , G Girotto  5 , S Lago  6 , E Smit  7 , G Ostoros  8 , W E E Eberhardt  9 , P Lishkovska  10 , S Lovick  11 , G Mariani  12 , A McKeown  13 , E Kilgour  11 , P Smith  12 , K Bowen  12 , A Kohlmann  12 , D J Carlile  12 , P A Jänne  14
Affiliations
Clinical Trial

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

J-C Soria et al. Ann Oncol. .

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.

Trial identifier: Clinicaltrials.gov NCT01750281.

Keywords: KRAS; MEK1/2; advanced non-small-cell lung cancer (NSCLC); docetaxel; metastatic disease; selumetinib.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Randomization and treatment. Data cut-off 27 January 2016. aInformed consent received. bAny reason not specifically recorded.
Figure 2.
Figure 2.
Kaplan–Meier estimates of progression-free survival for the overall population (A) and the KRAS wild-type population (B).
Figure 3.
Figure 3.
Kaplan–Meier estimates of overall survival for the overall population (A) and the KRAS wild-type population (B).
Figure 4.
Figure 4.
Best change in tumour size and associated duration of response for the SEL + DOC 60 (A), SEL + DOC 75 (B) and PBO + DOC 75 (C) cohorts.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Yeh TC, Marsh V, Bernat BA. et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res 2007; 13(5): 1576–1583. - PubMed
    1. Banerji U, Camidge DR, Verheul HM. et al. The first-in-human study of the hydrogen sulfate (Hyd-sulfate) capsule of the MEK1/2 inhibitor AZD6244 (ARRY-142886): a phase I open-label multicenter trial in patients with advanced cancer. Clin Cancer Res 2010; 16(5): 1613–1623. - PubMed
    1. Denton CL, Gustafson DL.. Pharmacokinetics and pharmacodynamics of AZD6244 (ARRY-142886) in tumor-bearing nude mice. Cancer Chemother Pharmacol 2011; 67(2): 349–360. - PMC - PubMed
    1. Roberts PJ, Stinchcombe TE.. KRAS mutation: should we test for it, and does it matter? J Clin Oncol 2013; 31(8): 1112–1121. - PubMed
    1. Davies BR, Logie A, McKay JS. et al. AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol Cancer Ther 2007; 6(8): 2209–2219. - PubMed

Publication types

MeSH terms

Associated data