Dr Bazhenova on the Need for Comprehensive Molecular Testing in Unresectable NSCLC

Lyudmila A. Bazhenova, MD, medical oncologist, professor, medicine, the University of California San Diego (UCSD) Moores Cancer Center, discusses key factors in the management of unresectable non–small cell lung cancer (NSCLC), emphasizing the importance of understanding and performing biomarker testing in this population.

Distinguishing between resectable and unresectable lung cancer is vital for selecting the most appropriate management approach, Bazhenova begins, adding that multidisciplinary collaboration allows for more informed decision-making. Although the current standard of care for patients with unresectable, stage III NSCLC is durvalumab (Imfinzi), this agent may not be advisable for use in patients expressing key oncogenic drivers, such as EGFR and ALK mutations, Bazhenova details.

Accordingly, comprehensive molecular testing is paramount for identifying which patients will benefit from available regimens, Bazhenova continues. Integrating DNA and RNA assessments into a routine molecular testing battery can be feasible and useful; however, it is important to understand the functional differences between DNA- and RNA-based tests to determine if 1 or both tests should be utilized. For example, information obtained from RNA-based testing can provide additional value for patients with gene fusions, Bazhenova says, noting that these can be prevalent in lung cancer. Understanding these nuances ensures more tailored and effective treatment strategies, Bazhenova emphasizes.

Lastly, it is critical to understand the challenges and limitations associated with the use of

cell-free DNA (cfDNA) as a diagnostic tool, Bazhenova states. Although cfDNA can be an effective, noninvasive diagnostic assay for patients with lung cancer, approximately 30% of cfDNA tests yield false negatives, she says. If liquid biopsy fails to identify a mutation, it is imperative not to halt the diagnostic journey, Bazhenova states. Performing additional tissue next-generation sequencing can potentially prevent clinicians from overlooking patients with underlying oncogenic drivers, she explains. This comprehensive approach ensures that patients receive the most accurate and beneficial diagnostic information, guiding personalized treatment plans for optimal outcomes, Bazhenova concludes.

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