Small Mutations, Big Impact

It’s routine to recommend molecular profiling for patients with advanced non-small-cell lung cancer (NSCLC), with the goal of better understanding the origins and potential treatment susceptibilities of their tumors. Many such patients are screened for mutations in oncogenes, tumor suppressor genes and their regulators – but what does this screening actually accomplish? Is it feasible to screen every NSCLC patient who enters the healthcare system, and if it is, do the patients truly benefit from it?

Figure 1. Frequency of genetic alterations in each screened oncogenic driver.

The French Cooperative Thoracic Intergroup (IFCT) conducted a one-year study to answer these questions and optimize the standard of care for NSCLC patients (1). The study included 17,664 patients who were screened for mutations in genes including EGFR, ALK, HER2, KRAS, BRAF and PIK3CA, all known drivers of oncogenesis (2). Ultimately, about half of the patients assessed exhibited at least one mutation (see Figure 1) – a significant fraction worthy of further investigation. The study authors also established that the existence of a mutation affected both the choice of first-line treatment (in 51 percent of patients with alterations) and its likelihood of success (37 percent of patients with mutations achieved an overall response, compared with 33 percent of those without). And not only first-line treatment was affected; second-line treatment improved (17 percent of patients with mutations responded, vs. 9 percent of those without), first-line progression-free survival increased (10 months in those with mutations vs. 7.1 months in those without), and overall survival increased (16.5 months in those with mutations vs. 11.8 months in those without). What can we take away from the French study? First, that routine molecular profiling of advanced NSCLC patients is feasible on a large scale. Second, and more importantly, that it’s worthwhile to do this kind of screening. Because the detection of even a single genetic mutation can have such a significant effect on patients’ treatment options, responses, and overall survival, examining the genetics of NSCLC patients may soon be a commonplace laboratory task.

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References

1. F Barlesi et al., “Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (ICFT)”, Lancet, S0140-6736(16)00004-0 (2016). PMID: 26777916. ClinicalTrials.gov, “French national observatory of the patients with non-small cell lung (nsclc) and molecular testings” (2016). Available at: http://1.usa.gov/1MrIRuL. Accessed April 12, 2016.

About the Author(s)

Michael Schubert

While obtaining degrees in biology from the University of Alberta and biochemistry from Penn State College of Medicine, I worked as a freelance science and medical writer. I was able to hone my skills in research, presentation and scientific writing by assembling grants and journal articles, speaking at international conferences, and consulting on topics ranging from medical education to comic book science. As much as I’ve enjoyed designing new bacteria and plausible superheroes, though, I’m more pleased than ever to be at Texere, using my writing and editing skills to create great content for a professional audience.

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