No Improvement in KRAS-Mutation Lung Cancer With MEK Inhibitor Plus Chemotherapy

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Approximately 25% of lung cancer cases are caused by a KRAS gene mutation.
Approximately 25% of lung cancer cases are caused by a KRAS gene mutation.

A combination treatment of mitogen-activated protein kinase MEK inhibitor and chemotherapy did not improve progression-free survival in patients with advanced lung cancer caused by a KRAS gene mutation. The clinical trial study was recently published in the Journal of the American Medical Association (JAMA).1

The study is a follow-up from a previous phase 2 study of 87 patients with KRAS mutant advanced non-small cell lung cancer in which progression-free survival was found to improve with combination treatment of the mitogen-activated protein kinase MEK inhibitor, selumetinib, and the chemotherapy drug, docetaxel.2

The recent study incorporated 510 patients with previously treated advanced KRAS mutant non-small cell lung cancer from 202 sites across 25 countries. A total of 254 patients were given a combination treatment of selumetinib and docetaxel for 74 days and 256 patients were given a placebo and docetaxel for 85 days, excluding dose interruption times. Progression-free survival did not improve with combination selumetinib and docetaxel treatment compared to placebo and docetaxel treatment.1

The overall median survival was 8.7 months in the combination group and 7.9 months in the placebo/docetaxel group. The median progression-free survival was 3.9 months in the combination group and 2.8 months in the placebo/docetaxel group. Adverse effects at grade 3 or higher were more frequent in the combination group (67%) compared with the placebo/docetaxel group (45%).

Approximately 25% of lung cancer cases are caused by a mutation in the KRAS gene. Yet, there are no effective treatments for this sub-group of lung cancer patients. "KRAS mutations represent the largest genomically defined subset of lung cancer. There remains a great need to develop effective therapies for this subset of patients and the findings from the present study further highlight this,” conclude the investigators.

References

1. Janne PA, van den Heuvel MM, Barlesi F, et al. Selumetinib plus docetaxel compared with docetaxel alone and progression-free survival in patients with KRAS-mutant advanced non–small cell lung cancer: the SELECT-1 Randomized Clinical Trial. JAMA. 2017;317(18):1844-1853.

2. Janne PA, Shaw AT, Pereira JR, et al. Selumetinib plus docetaxel for KRAS-mutant advanced non-small-cell lung cancer: a randomised, multicentre, placebo-controlled, phase 2 study. Lancet Oncol. 2013;14(1):38-47. 
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