SELECT-2: a Phase II, double-blind, randomised, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment for patients with advanced or metastatic non-small cell lung cancer.

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/m(2) (SEL+DOC 60; SEL+DOC 75), or placebo plus docetaxel 75 mg/m(2) (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.