In catching up with breast cancer and several hematologic malignancies, non–small cell lung cancer (NSCLC) has made recent advances in targeting genomic mutations that will provide us with the ability to offer more targeted treatment options. Researchers at Massachusetts General Hospital Cancer Center have developed a multiplexed PCR-based assay (SNaPshot) to simultaneously identify >50 mutations in several key NSCLC genes.1 In this study, the SNaPshot assay identified 51% of tumors as having at least 1 mutation, most commonly in KRAS (24%), EGFR (13%), PIK3CA (4%), and translocations involving anaplastic lymphoma kinase (ALK; 5%). Several associations were observed between genotypes and clinical characteristics. Many institutions across the country are developing their own unique version of this assay. This genotyping has significant utility in influencing treatment decisions and directing patients toward relevant clinical trials.
One new subset of NSCLC is the presence of the ALK fusion oncogene, which was recently studied in a phase 1 clinical trial.2 The study looked at the ALK tyrosine kinase inhibitor crizotinib, which revealed significant activity in patients with ALK-positive NSCLC. On August 26, 2011, the US Food and Drug Administration (FDA) granted accelerated approval to crizotinib for patients with locally advanced or metastatic NSCLC that is ALK-positive as detected by an FDA-approved test, Vysis ALK Break-Apart FISH Probe Kit.3 Crizotinib was initially developed as a MET inhibitor but was subsequently found to have inhibitory activity against the EML4-ALK fusion protein.4 Currently, resistance mechanisms are being studied, and another class of drugs, heat shock protein inhibitors, may have a role in this subset of resistant patients.
The introduction of targeted treatment options provides patients with a more individualized approach to patient care. From the nursing perspective, the movement toward more individualized care brings with it both improved outcomes and challenges. We are able to offer patients treatment options with increased efficacy potential. As a nurse, I see this instill confidence in patients with their healthcare team and increase hopefulness for a response to treatment. It also provides patients with time in which we hope that research will learn more about drug resistance and provide more treatment options. Along with the positive aspects associated with more individualized care, we also experience challenges. The recent research advances have been capitalized on by the media. Patients are able to easily find pieces of information on the Internet and television, but the harsh reality of success is dramatized. Crizotinib is approved for ALK-positive NSCLC patients, who represent about 3% to 4% of the entire NSCLC population. 5 EGFR mutations account for about 15% of the NSCLC population. There is much work to be done before we are able to find specific mutations or markers that can help us direct individualized care for each patient.
- Sequist LV, Heist RS, Shaw AT, et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol. 2011;22:2616-2624.
- Shaw AT, Yeap BY, Solomon BJ, et al. Effect of crizotinib on overall survival in patients with advanced nonsmall- cell lung cancer harbouring ALK gene rearrangement: a retrospective analysis. Lancet Oncol. 2011; 12:1004-1012.
- National Cancer Institute. FDA approval for crizotinib. www.cancer.gov/cancertopics/druginfo/fda-crizotinib. Accessed January 27, 2012.
- Govindan R. Hope without hype: EML4-ALK inhibition for treatment of lung cancer. Lancet Oncol. 2011;12:983-984.
- Shaw AT, Yeap BY, Mino-Kenudson M, et al. Clinical features and outcome of patients with nonsmall-cell lung cancer who harbor EML4-ALK. J Clin Oncol. 2009;27:4247-4253.