Case Study: Treating KRAS-Mutant Adenocarcinoma

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Moderator Corey J. Langer, MD, describes a 46 year-old woman with KRAS mutation positive non-small-cell lung cancer (NSCLC) that has been identified to be primarily adenocarcinoma histology. Following approximately 6 months of treatment with bevacizumab, the patient is beginning to progress. Unfortunately, at this point, no approved targeted therapies are available specifically for patients with KRAS-mutant NSCLC, explains Roy S. Herbst, MD, PhD. However, a number of clinical trials are exploring possible treatment options.

MEK inhibitors represent a promising treatment approach for patients with KRAS-mutant NSCLC, explains Herbst believes. A phase II trial examined the MEK inhibitor selumetinib in combination with docetaxel compared to docetaxel alone for patients with advanced KRAS-mutant NSCLC. In this trial, progression-free survival was significantly prolonged from 2.1 months with docetaxel to 5.3 months with the combination. Additionally, a promising trend toward an improvement in overall survival was also noticed with the combination, notes Herbst.

In addition to the combination with docetaxel, the ongoing phase II BATTLE-2 trial is exploring selumetinib plus the AKT inhibitor MK-2206. KRAS mutation status is being considered in the randomization of this trial. Furthermore, Herbst notes, patients with KRAS mutations are also receiving investigational treatment with PD-1 and PD-L1 antibodies, which seem to be generating promising results.

In addition to KRAS mutations, other actionable mutations are generating interest in NSCLC. The BRAF V600E mutation occurs in approximately 2% of patients with NSCLC, explains Anne S. Tsao, MD. Additionally, in early phase trials, the BRAF inhibitor dabrafenib has demonstrated promising data in this population.

The Lung Cancer Mutation Consortium has gradually begun to parse NSCLC into defined subpopulations based on actionable mutations, notes Tsao. At this point, approximately 67% of lung tumors have an identifiable driver mutation. However, whether or not these mutations are actionable remains unclear, Tsao adds.