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David S. Ettinger, MD, FACP, FCCP


Can Driver Genetic Alterations Predict Survival in Advanced Lung Adenocarcinoma?

By: Kayci Reyer
Posted: Tuesday, March 8, 2022

According to research presented in BMC Pulmonary Medicine, patients with advanced lung adenocarcinoma may benefit from undergoing an expansive mutation analysis at diagnosis. Driver genetic alterations in the EGFR, KRAS, BRAF, or HER2 genes may impact survival outcomes among this patient population. Giuseppe Palmieri, MD, PhD, of the Institute of Genetic and Biomedical Research in Italy, and colleagues reported these real-life study findings, which were based on patients from the Italian island of Sardinia, in BMC Pulmonary Medicine.

“In addition to its predictive value for addressing targeted therapy approaches, the assessment of [a] more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced [lung adenocarcinoma] patients,” concluded the investigators.

The study included 1,282 Sardinian patients who had undergone genetic testing between January 2011 and July 2016. Overall, 13.7%, 21.3%, and 3% of patients were found to have EGFR, KRAS, and BRAF mutations, respectively. A total of 4.7% of patients had ALK rearrangements, and 2% had MET amplifications.

At a median follow-up of 46 months, survival was significantly longer for patients with EGFR mutations in exons 18 to 21 than for those without such mutations (P < .0001), an outcome expected due to the increased sensitivity to anti-EGFR tyrosine kinase inhibitor therapy. However, survival was significantly lower for patients with KRAS mutations (P = .0058). An association was noted between the presence of EGFR T790M–mutated alleles at baseline analysis and inferior survival. Among 193 patients who tested positive for EGFR T790M–mutated alleles, 26 (13.5%) experienced a significantly shorter survival than those without these mutated alleles (8.7 months vs. 47.4 months).

“Data from future real-life studies based on a more comprehensive molecular classification at the time of diagnosis of the advanced disease are constantly necessary to better evaluate the real impact of specific genetic alterations and their corresponding targeted therapies in patients with lung cancer,” the study authors noted.

Disclosure: For full disclosures of the study authors, visit

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