In contrast with docetaxel alone, the addition of selumetinib to docetaxel did not significantly improve progression-free survival, overall survival, or the overall response rate of patients receiving second-line therapy for KRAS-mutant non-small cell lung cancer (NSCLC), according to a study presented at the European Society for Medical Oncology (ESMO) 2016 Congress.1

Selumetinib is an oral, potent, and selective MEK1/2 inhibitor. A phase 2 trial demonstrated that adding selumetinib to second-line docetaxel significantly improved progression-free survival and overall response rate versus docetaxel. Researchers therefore evaluated the efficacy and safety of the combination in a phase 3 trial.

For the international, double-blind, phase 3 SELECT-1 study (ClinicalTrials.gov Identifier: NCT01933932), investigators enrolled 510 patients with locally advanced or metastatic NSCLC and a centrally confirmed KRAS mutation. Participants were randomly assigned to receive second-line treatment with docetaxel intravenously on day 1 plus selumetinib orally twice daily or placebo of each 21-day cycle. Patients also received granulocyte-colony stimulating factor (G-CSF).

Researchers found that 20.1% of patients treated with selumetinib and docetaxel achieved a response versus 13.7% of those who received docetaxel plus placebo (odds ratio [OR], 1.61; 95% CI, 1.00-2.62; P = .051).

Median progression-free survival was 3.9 months with selumetinib plus docetaxel compared with 2.8 months with placebo plus docetaxel (hazard ratio [HR], 0.93; 95% CI, 0.77-1.12; P = .44). There was also no significant difference in overall survival between selumetinib and placebo (8.7 months versus 7.9 months, respectively; HR, 1.05; 95% CI, 0.85-1.30; P = .64).

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The safety profile of selumetinib and docetaxel was consistent with previous reports. Grade 3 or worse adverse events, serious adverse events, and adverse events leading to hospitalization were more frequently reported with selumetinib than with placebo.                              

Reference

  1. Janne PA, Van den Heuvel M, Barlesi F, et al. Selumetinib in combination with docetaxel as second-line treatment for patients with KRAS-mutant advanced NSCLC: Results from the phase III SELECT-1 trial. Paper presented at: European Society for Medical Oncology (ESMO) 2016 Congress; October 7-11, 2016; Copenhagen, Denmark.