Contemporary Issues in NSCLC

Lung cancer remains the number one cancer killer in both men and women, with more deaths attributable to lung cancer than breast, prostate, and colorectal cancers combined.[1] The 5-year survival rate is dismal at about 17%,[2] but recent advances in lung cancer treatment offer hope for improvement of this statistic. Lung cancer is primarily divided into two subtypes: small cell and non–small-cell, with non–small-cell disease representing approximately 85% of cases.[3] The latest breakthroughs in lung cancer have been developed in non–small-cell lung cancer (NSCLC), and Elizabeth Waxman’s article provides a comprehensive overview of contemporary therapies for this population.

Current treatment strategies for advanced NSCLC are predicated on histology, the presence of certain biomarkers, and the role of maintenance therapy. Two prospective phase III clinical trials have documented improved survival with the use of pemetrexed (Alimta) in patients with non–squamous-cell histology and lack of efficacy in those with squamous histology: the Scagliotti (2008) study[4] referenced by Ms. Waxman, and the Ciuleanu (2009) maintenance trial.[5] Pemetrexed is therefore only indicated in patients with non-squamous histology. In addition to pemetrexed, bevacizumab (Avastin) is also indicated only for use in non-squamous NSCLC. It is contraindicated in the squamous-cell population due to its association with major hemoptysis.[6]

Biomarker assessment has become an essential tool in the treatment selection process for NSCLC, including evaluation for EGFR and KRAS mutations as well as EML4-ALK translocations. NSCLC patients who harbor an EGFR mutation have high rates of response to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) such as erlotinib (Tarceva), with improved progression-free survival and less hematologic toxicity when given front-line vs standard chemotherapy.[7] Secondary acquired EGFR mutations such as T790M, however, may be associated with EGFR-TKI resistance, and the presence of a KRAS mutation may also indicate greater resistance to EGFR-TKIs.[8] Crizotinib (Xalkori) was given accelerated FDA approval in August 2011 for use in ALK-positive NSCLC based on early-phase data showing high response rates. A phase III study to evaluate survival is ongoing. Future avenues of exploration include an array of targets for drug development such as BRAF, IGFR-1R, mTOR, and MEK.

Finally, maintenance therapy has become a valuable asset in management of patients with NSCLC. Both erlotinib and pemetrexed are FDA-approved for this indication, but the National Comprehensive Cancer Network (NCCN) and American Society of Clinical Oncology (ASCO)[9] guidelines offer alternative options as well. Maintenance therapy should be continued until evidence of disease progression or unacceptable toxicity.[8]

Over the past decade, the treatment of NSCLC has evolved from a few generalizable chemotherapy regimens to a sophisticated paradigm of options based on specific tumor characteristics. Oncology nurses should find that the Waxman article provides a solid foundation of state-of-the-art treatment options in NSCLC.

Financial Disclosure:Suzanne Walker serves on the speakers bureau of Eli Lilly, Inc.

References:

References

1. American Cancer Society: Cancer Facts & Figures 2012. American Cancer Society, Atlanta, 2012. Available at http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-031941.pdf. Accessed on July 18, 2012.

2. Fast Stats: An interactive tool for access to SEER cancer statistics. Surveillance Research Program, National Cancer Institute. Available at http://seer.cancer.gov/faststats. Accessed on June 27, 2012.

3. SEER Cancer Statistics Review, National Cancer Institute. Available at http://seer.cancer.gov/csr/1975_2009_pops09/results_merged/sect_15_lung_bronchus.pdf. Accessed on June 27, 2012.

4. Scagliotti, GV, Parikh, P, von Pawel, J, et al: Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small cell lung cancer. J Clin Oncol 26(21):3543–3551, 2008.

5. Ciuleanu T, Brodowicz T, Zielinski C, et al: Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: A randomised, double-blind, phase 3 study. Lancet 374(9699):1432–1440, 2009.

6. Johnson DH, Fehrenbacher L, Novotny WF, et al: Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small cell lung cancer. J Clin Oncol 22(11):2184–2191, 2004.

7. Bria E, Milella M, Cuppone F, et al: Outcome of advanced NSCLC patients harboring sensitizing EGFR mutations randomized to EGFR tyrosine kinase inhibitors or chemotherapy as first-line treatment: A meta-analysis. Ann Oncol 22(10):2277–2285, 2011.

8. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer [v.3.2012]. Available at http.www.nccn.org.

9. Azzoli CG, Temin S, Aliff T, et al: Focused update of 2009 American Society of Clinical Oncology clinical practice guideline update on chemotherapy for stage IV non-small-cell lung cancer. J Clin Oncol 29(28):3825–3831, 2011.