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Molecular analysis of NSCLC established in community hospital network
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CHICAGO — It is possible to routinely conduct high-quality molecular analysis of non–small cell lung cancers in local community hospitals, which could make molecular testing available to more patients in hospitals closer to patients’ homes, according to a multicenter study.
Although personalized treatment strategies for genetically stratified NSCLC subgroups have the potential to improve patient outcomes, the primary obstacle remains how to employ high-quality molecular diagnostics in everyday clinical practice and beyond highly specialized academic centers.
“Several of the most effective drugs used to treat advanced non–small cell lung cancer today are only effective in patients whose tumors have specific genetic markers,” Thomas Zander, MD, of the University Hospital in Cologne, Germany, said in a press release. “Because of advances in molecular testing technologies for these biomarkers and the ease of doing this testing today in many laboratories, our research shows that state-of-the-art personalized medicine is possible in community hospitals, and not just in advanced academic medical centers.”
After review of the local ethics committee, Zander and colleagues established a molecular screening network — the Network Genomic Medicine Lung Cancer — which involved several non-academic community hospitals in the Cologne-Bonn area and included about 2.5 million residents.
In this study, 1,782 samples of NSCLC were collected in the Cologne-Bonn area, 77% of which was found to be suitable for molecular analysis. Lung adenocarcinoma was screened centrally for ALK translocations, mutations in KRAS, EGFR, BRAF and PIK3CA and for amplification of ERBB2. Squamous cell carcinoma was also examined for FGFR1 amplifications.
After molecular analysis, samples from lung adenocarcinoma patients exhibited distinct frequencies of genetic lesions, including KRAS (32%), EGFR (13%), ALK (3%), BRAF (2%), PIK3CA (2%), ERBB2 (2%). EGFR mutations were observed to be highly enriched in the lepidic and micropapillary subtype of lung adenocarcinoma (30%-32%), while the solid subtype only exhibited a minor amount of the tested oncogenic lesions. Among patients with squamous cell cancers, 15% of tumors harbored FGFR1 amplification.
“In patients with FGFR1 amplication, a majority demonstrated more than five copies of FGFR1,” Zander said during a press conference. “In some cases, patients demonstrated clusters of FGFR1 with more than 15 to 30 copies — the clinical implication of these different amplification patterns remains to be studied.”
According to Zander, 40% of NSCLC samples harbored genetic mutations that could be targeted, and 75% of all patients with an EGFR-mutation received erlotinib or gefitinib, mostly first-line.
“Survival of patients with an EGFR-mutation was significantly longer with a median OS of about 3 years, which might be due to the relatively broad use of second-generation EGFR-targeted drugs in cases with resistance to erlotinib or gefitinib,” Zander said.
For more information:
Zander T. Abstract #CRA10529. Presented at: the 2012 American Society of Clinical Oncology Annual Meeting; June 1-5, 2012; Chicago.
Disclosure: The researchers reported consulting/advisory positions, as well as research funding, from AstraZeneca, Boehringer Ingelheim, Lilly, Novartis and Roche/Genentech.
Perspective
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Sylvia Adams, MD
This large feasibility trial shows that it is feasible in the community setting to do molecular testing of cancers in real time to identify a large subgroup of patients who harbor these oncogenic mutations and that results can guide treatment selection. This is important for oncologists to treating patients because it confirms that we can choose the most appropriate target therapy for patients, we can enroll patients into the appropriate targeted trials, and, most importantly, that there is meaningful change in outcomes when we select patients.
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