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.
- 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.