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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.

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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

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