More biomarkers should be included in the standard molecular testing for lung adenocarcinoma to improve patients’ prognosis and survival, results of the LCMC II (Lung Cancer Mutation Consortium II) study suggest.

“In addition to EGFR mutation and ALK rearrangement, we analyzed the frequency and clinical impact of a broader set of genetic alterations in lung adenocarcinoma. These include point mutations in AKT1, BRAF, ERBB2, KRAS, MAP2K1, PIK3CA and NRAS, as well as MET amplification, RET and ROS1 rearrangements, and PTEN and MET expression,” explained lead author Dr. Dara Aisner of the University of Colorado, CO, US. “Additional mutation data such as TP53 and PTEN were provided as available.” [ASCO 2016, abstract 11510]

A total of 875 patients with confirmed stage IV lung adenocarcinoma were recruited in this study. The patients were either prescribed standard treatment based on molecular testing results, or recommended to participate in clinical trial of agents specific for certain alterations.

The most frequent driver alterations in the study were KRAS mutation (25 percent), sensitizing EGFR mutation (10 percent) and ALK rearrangement (4 percent). AKT1 mutation was not detected, while other alterations were present in 0.5 to 3 percent of the studied population. “The remaining 44 percent had no detectable mutations by genotyping,” reported Aisner. “However, initial results from immunohistochemical analysis revealed MET expression and PTEN loss in 59 percent and 15 percent of the patients, respectively. The data are currently pending central review.”

“Smokers who carried detectable driver mutations had significantly longer overall survival [OS] than those who did not [median, 2.7 vs 1.6 years; p=0.008]. Therefore, identification of driver mutations is important in lung adenocarcinoma patients who have a smoking history,” she stressed. “In addition, KRAS mutations tended to be associated with a worse prognosis in never smokers.”

“Doubleton mutations were reported in 4.1 percent of the patients, with the majority having co-occurring MET amplification/KRAS mutation, PIK3CA/KRAS mutations, MET amplification/EGFR mutation or PIK3CA/EGFR mutations,” noted Aisner.

“TP53 mutations might confer a worse prognosis in patients harbouring sensitizing EGFR mutations who were treated with targeted therapy [median OS, 2.9 years vs not reached in counterparts without TP53 mutations; p=0.02],” she added. “TP53 mutations are likely under-reported, because the positivity rate was 48 percent by next-generation sequencing, but only 8 percent by non-next-generation sequencing in our study.”