Genetic testing in metastatic non-small cell lung cancer (NSCLC) patients and subsequent molecular biomarker guided therapy is societally cost-effective compared to a chemotherapy treatment approach without molecular testing.
Genetic testing in metastatic non-small cell lung cancer (NSCLC) patients and subsequent molecular biomarker guided therapy is societally cost-effective compared to a chemotherapy treatment approach without molecular testing. This is according to a study published in the Journal of Thoracic Oncology.
Several targeted agents are now approved for metastatic NSCLC by the US Food and Drug Administration (FDA) as about 9.5% and 4% of those diagnosed with the disease harbor a mutation in either epidermal growth factor receptor (EGFR), or have a rearrangement in the anaplastic lymphoma kinase (ALK) gene, respectively. Erlotinib (Tarceva) and afatinib (Gilotrif) are two currently approved EGFR-targeted small molecule inhibitors. Two ALK-targeting oral therapies, crizotinib (Xalkori) and ceritinib (Zykadia), used to treat those NSCLC tumors harboring the ALK mutation are also approved by the FDA.
Still, while NSCLC patients with either of these two mutation types have higher response rates and longer progression-free survival (PFS) when treated with the appropriate targeted therapy compared to the standard of care chemotherapy regimen (platinum-based chemotherapy doublet), only a relatively small percentage of patients have been shown to undergo genetic tumor testing.
While clinical guidelines recommend that most patients undergo genetic screening for these mutations in practice, only about 12% of hospitals in the US used EGFR biomarker testing on NSCLC as late as 2010, according to a 2013 study. Two issues with applying biomarker information to a patient’s treatment are relatively slow genetic biomarker turn around times and having an insufficient amount of tumor sample to assay--both of which lead to the start of a chemotherapy regimen.
Dorothy Romanus, PhD, of the Massachusetts General Hospital and Harvard University in Boston, and colleagues created a model to estimate life expectancy and cost scenarios for treatment-naive metastatic NSCLS patients: no genetic testing and treatment with chemotherapy, two different chemotherapy regimens with concurrent biomarker testing in which a patient was switched from chemotherapy to a targeted therapy, and treatment initiation only following the results of the genetic test. Surveillance, Epidemiology, and End Results (SEER) Medicare data was used to model the natural history of the disease.
The modeling results demonstrate that the incremental cost-effectiveness ratio (ICER) for the scenario of testing, and using the results to make a decision on treatment compared to no test and chemotherapy treatment equated to a $136,000 per quality-adjusted life-year (QALY) gained. Without an adjustment for quality of life, the test and treat approach resulted in $102,000 per life-year gained compared to no genetic testing and treatment with chemotherapy. Overall, the ICER for the test and treat scenario compared to no genetic testing varied from $124,000 to $157,000 per additional QALY. The modeling outcomes varied depending on the cost of genetic testing.
The approach of starting chemotherapy concurrently with testing and switching to a targeted agent immediately when test results were available resulted in better QALY outcomes and life years compared to completing an entire course of chemotherapy before switching to a targeted drug.
This analysis supports the value of multiplexed testing for EGFR and ALK gene rearrangements followed by molecularly-guided therapy in decisions surrounding coverage of related testing and targeted therapy,” said Romanus in a statement. “Ensuring patient access to said breakthrough therapies through lower cost sharing is key. As evidence evolves and testing for a wider range of known mutations in NSCLC enters routine care, it will be increasingly important for future economic analyses to consider multiplexed testing for multiple mutations in tandem to fully appreciate the value of personalized treatment in this disease."
The study was sponsored by the Cancer Outcomes Research Training Program at the National Cancer Institute.