Combination treatment for advanced lung cancer does not improve survival

Among patients previously treated for a type of advanced lung cancer, use of a combination treatment did not improve progression-free or overall survival, according to a study published by JAMA.

Genotype-directed targeted therapy is the standard of care for patients with advanced non-small cell lung cancer (NSCLC). However, there are currently no targeted therapies specifically approved for patients with lung cancers related to a mutation in the KRAS gene, which are detected in approximately 25 percent of lung adenocarcinoma patients.

Pasi A. Jänne, M.D., of the Dana-Farber Cancer Institute, Boston, and colleagues randomly assigned 510 patients with previously treated advanced KRAS-mutant non-small cell lung cancer to the drug docetaxel plus selumetinib or docetaxel and placebo. In a phase 2 study (n = 87), selumetinib in combination with docetaxel improved progression-free survival for patients with KRAS-mutant advanced NSCLC. The current study was conducted at 202 sites across 25 countries.

Median duration of randomized treatment, excluding dose interruption time, with selumetinib or placebo was 74 days in the selumetinib + docetaxel group and 85 days in the placebo + docetaxel group. The researchers found that selumetinib + docetaxel did not improve progression-free survival or overall survival compared with placebo + docetaxel. Median progression-free survival was 3.9 months in the selumetinib + docetaxel group and 2.8 months in the placebo + docetaxel group, whereas median overall survival was 8.7 months in the selumetinib + docetaxel group vs 7.9 months in the placebo + docetaxel group. Grade 3 or higher adverse events were more frequent with selumetinib + docetaxel (67 percent) than placebo + docetaxel (45 percent).

Limitations of the study are noted in the article.

"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," the authors write.