Background
Multiple Treatment Options are Available for Advanced or Metastatic NSCLC1
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as erlotinib, represent an effective, targeted therapy for a select group of patients with advanced non-small cell lung cancer (NSCLC). The table below summarizes commonly used agents for treating advanced NSCLC.
Identifying appropriate therapy for patients is key to improving patient outcomes.
Often, patient characteristics are used to guide EGFR-TKI therapy. Certain characteristics are associated with increased response rate and longer survival in the overall NSCLC patient population such as:2
- Asian ethnicity
- Female
- Never smoker
- Adenocarcinoma tumor histology
In addition to patient characteristics, molecular tests are utilized to aid in clinical decision making. Molecular tests require a tumor tissue sample for analysis. There are challenges that exist with tumor sample analysis, such as:
The low availability of tissue biopsy material
- Collection of biopsy samples from patients is invasive3
- Patients with comorbidities and poor performance status may not be able to provide tissue samples3
- The average percentage of patients providing tumor samples in key EGFR-TKI trials in NSCLC is only 25-30%4
The biopsy sample may not be representative of the tumor
- NSCLC tumors are heterogeneous and EGFR expression can be different between the primary tumor and metastases5,6
- Genomic instability may cause tumor cells to change between time of diagnosis and treatment5-7
Technical challenges exist for molecular tests
- Tests such as IHC and FISH lack fixed objective definitions of “positivity” and their testing methods require standardization5
- Test performance varies because of differences in biopsy preservation methods5,8
Unlike other molecular tests that require a tumor tissue sample for analysis, VeriStrat® is a proteomic test that characterizes the protein content of serum.
VeriStrat uses matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) which is an innovative technology that reliably characterizes protein content to assist with treatment decisions.
A brief pictorial of the VeriStrat process is below.
- Serum samples are analyzed in triplicate with MALDI-TOF MS, resulting in raw spectra
- Raw spectra are processed using Biodesix proprietary technology to generate comparable spectra
- Processed spectra are then analyzed using the VeriStrat classifier and labeled as either VeriStrat Good or VeriStrat Poor
- If the replicates agree, the respective label is reported, otherwise, the resulting label is indeterminate
Download the VeriStrat Scientific Presentation (PDF)
References
1. NCCN Clinical Practice Guidelines in Oncology™: Non-Small Cell Lung Cancer, v.2.2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/nscl.pdf.
2. Bonomi PD, Buckingham L, Coon J. Selecting patients for treatment with epidermal growth factor tyrosine kinase inhibitors. Clin Cancer Res. 2007;13:s4606-s4612.
3. Cox JE, Chiles C, McManus CM, Aquino SL, Choplin RH. Transthoracic needle aspiration biopsy: variables that affect risk of pneumothorax. Radiology. 1999;212:165-168.
4. Soria JC, Application and limitation of biomarker analysis: session discussion. Presented at: 44th ASCO Annual Meeting; May 30-June 3, 2008; Chicago, IL.
5. Eberhard DA, Giaccone G, Johnson BE. Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting. J Clin Oncol. 2008;26:983-994.
6. Moroni M, Veronese S, Sartore-Bianchi A, Artale S, Siena S. Controversial evaluation of EGFR protein and gene status in predicting response to anti-EGFR monoclonal antibodies in metastatic colorectal cancer: a case report and review of the literature. Targeted Oncology. 2008;3:127-130.
7. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70.
8. Galleges Ruiz MI, Floor K, Steinberg SM, et al. Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients. Br J Cancer. 2009;100:145-152.