Evolving and Expanding Treatment Options in NSCLC

Lung cancer remains the leading cause of cancer death in the United States, with only 16% of patients living 5 years or more after they are diagnosed. Non–small-cell lung cancer (NSCLC) accounts for the majority of cases, with most of those cases being diagnosed in advanced stages.[1] Encouragingly, the overall treatment of NSCLC has undergone many changes in the last few years. While NSCLC remains a disease that is difficult to treat, advances are being made. From early-stage to advanced NSCLC, clinical trials in recent years have introduced treatment options that are having an impact on patient survival outcomes.

While treatment with chemotherapy for advanced NSCLC has long been accepted as the standard of care, use of chemotherapy in the neoadjuvant, adjuvant, and combined-modality settings for earlier-stage NSCLC has also proven to enhance survival. Clinical trials have provided survival data in both the neoadjuvant and adjuvant settings for patients with stages I to IIIA disease. This means that nurses are administering chemotherapy to more patients with earlier-stage NSCLC than ever before.

In 2003 and 2004, the age of molecularly targeted therapy in the treatment of advanced or recurrent lung cancer became a reality as agents such as gefitinib (Iressa) and erlotinib (Tarceva), both oral tyrosine kinase inhibitors that target the epidermal growth factor receptor (EGFR), were approved for use in advanced NSCLC in the second-line/third-line monotherapy settings. Based on the ever-expanding scientific knowledge about tumor biomarkers and genotypes, the most efficacious use of molecularly targeted agents in NSCLC continues to evolve. Clinical trial data now support the recommendation for use of erlotinib as monotherapy in the first-line setting for patients with NSCLC who have known EGFR mutations.[2] Crizotinib (Xalkori), a different molecularly targeted kinase inhibitor, was approved by the US Food and Drug Administration (FDA) in the spring of 2012 as monotherapy for patients who have advanced NSCLC and are anaplastic lymphoma kinase (ALK)-positive.[2]

Historically, triplet chemotherapy regimens did not prove to increase survival in advanced NSCLC, and the ceiling of doublet chemotherapy effectiveness seemed to have been reached. However, in 2006 the FDA approved bevacizumab (Avastin), a monoclonal antibody targeting vascular endothelial growth factor (VEGF), to be combined with paclitaxel and carboplatin for treatment of advanced NSCLC. The decision was based on an increase in overall survival data and showed that adding a third therapy (specifically a molecularly targeted therapy) to cytotoxic chemotherapy could prove efficacious in advanced NSCLC (excluding squamous cell histology, due to increased bleeding events in that population).[3] With the addition of molecularly targeted drugs to the armamentarium of cytotoxic chemotherapy treatments, we began to see an impact on overall survival. Expanding treatment options such as using switch or continuance-maintenance therapy with either cytotoxic chemotherapy or molecularly targeted therapy may also improve outcomes for certain patients with advanced NSCLC.

In the arena of advanced NSCLC, treatment options continue to evolve as methods of individualizing and personalizing systemic treatments are discovered. There is no longer a “one treatment fits all” approach in advanced NSCLC. As our physicians and scientists learn more about how to apply the individual characteristics of a patient’s tumor to the drugs we have available and those we are studying in clinical trials, we hope that the advances will continue to make a broader impact on patient survival.

The article by Elizabeth Waxman provides a clinically relevant and timely update as the treatment paradigm for NSCLC continues to evolve. Presenting the latest clinical trial data for systemic treatment of NSCLC from stage I to stage IV disease, Ms. Waxman discusses how the pertinent data are translated into treatment options. An overview is provided to show how personalized treatment decisions are made for patients with advanced NSCLC based on histology, mutation analysis, biomarkers, and individualized factors such as performance status. Additionally, she discusses the relatively new concepts of switch and continuance-maintenance therapy. This excellent overview article succinctly brings nurses up to date with the latest data related to the treatment of NSCLC.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

References

1. Siegel R, Naishadham D, Jemal A: Cancer statistics, 2012. CA Cancer J Clin 62(1):10–29, 2012.

2. National Comprehensive Cancer Network (2012): NCCN Clinical Practice Guidelines in Oncology: Non–Small-Cell Lung Cancer [v2.2012]. Available at http://www.nccn.org/professionals/physician_gls/pdf/nscl/pdf. Accessed on June 24, 2012.

3. Sandler A, Gray R, Perry MC, et al: Paclitaxel-carboplatin alone or with bevacizumab for non-small cell lung cancer. N Engl J Med 355(24):2542–2550, 2006.