Multiplex Genetic Testing Drives Lung Cancer Treatment Decisions

Simultaneous genetic testing for oncogenic drivers in lung cancer may help clinicians choose the best treatment

medwireNews: Multiplex testing for oncogenic driver mutations can match lung cancer patients to genotype-targeted treatments, potentially improving survival, US researchers say.

The proof of principle study included at least one genetic test in 1007 lung cancer patients, with a full 10-gene screening panel completed for 733 patients, explain Mark Kris, from Memorial Sloan Kettering Cancer Center in New York, and co-authors.

As reported in JAMA, 64% of the patients had at least one oncogenic driver but just 3% had more than one mutation identified.

“To our knowledge, this is the first study to show the lack of overlap between oncogenic drivers, only because we tested as many tumors as possible for all drivers”, the researchers explain.

In all, 25% tested positive for K-Ras, 17% for EGFR mutations sensitive to tyrosine kinase inhibitor treatment and 8% for an ALK rearrangement. A further 4% of patients tested positive for non-sensitising EGFR mutations, 3% for ERBB2 and 2% for BRAF, while fewer than 1% of patients carried mutations of PIK3CA, NRAS or MEK1 or the MET amplification.

The testing allowed researchers to match a current treatment to the patient’s genotype or to direct them to a clinical trial. For example, 18 patients were able to access BRAF inhibitor therapy earlier than otherwise would have been possible.

The team emphasises that, because the study was not a randomised trial designed to show survival outcomes, the results should be taken as a “proof of concept” for the use of multiplex screening to guide targeted treatment.

Nevertheless, data available for 938 patients revealed that survival significantly differed between the 260 patients with an oncogenic driver who received a targeted treatment compared with the 318 patients with a driver but no targeted treatment and the 360 patients for whom no oncogenic driver was identified (median 3.5 vs 2.4 and 2.1 years, respectively).

Propensity modelling confirmed a significant decreased risk of death in patients given genotype-directed treatment compared with patients with an oncogenic driver but no targeted therapy, with a hazard ratio of 0.69.

Genotype-directed treatment continued to be associated with improved survival even after excluding patients with EGFR orALK-positive disease, the team adds.

In an accompanying editorial, Boris Pasche, from Wake Forest University in Winston Salem, North Carolina, and Stefan Grant, from the University of Birmingham in Alabama, say that “the approach presented in this study should be used as a starting point for the implementation of a new clinical trial model employing large multicenter clinical trials offering experimental treatment for multiple targets.”

They conclude: “Although much remains to be done, the incorporation of genomic medicine into the study and treatment of lung cancer represents, at the very least, the end of the beginning for the care of these and other patients with cancer.”


Kris M, Johnson B, Berry L, et al.Using Multiplexed Assays of Oncogenic Drivers in Lung Cancers to Select Targeted Drugs. JAMA 2014; 311: 1998–2006. doi:10.1001/jama.2014.3741

Pasche B, Grant SC. Non–Small Cell Lung Cancer and Precision Medicine A Model for the Incorporation of Genomic Features Into Clinical Trial Design. JAMA 2014; 311: 1975–1976. doi:10.1001/jama.2014.3742

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