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Report by the Lung Cancer Mutation Consortium (LCMC)

Reviewer: James R. Jett, M.D., National Jewish Health, Denver, Colorado

This report by the Lung Cancer Mutation Consortium (LCMC) is a landmark study of the molecular mutations in patients with stage IV adenocarcinoma of the lung from 2009-2012. Tumors from 1,007 patients were tested for at least one gene, and 733 patients were tested for all ten genes of interest. An actionable driver mutation was identified in 466 of 733 patients (64%). The most common driver mutations were: KRAS (25%); sensitizing EGFR (17%); ALK rearrangements (8%); other EGFR (4%); ERBB2 (3%); BRAF (2%). Two or more mutations were identified in 3% of tumors. The median survival of patients with a sensitizing mutation that were treated with a targeted therapy directed at the specific mutation was 3.5 years. Median survival was only 2.4 years in those with a sensitizing mutation who did not receive targeted therapy.

This study demonstrates the feasibility and importance of performing multiplex gene mutation testing in patients with stage IV adenocarcinoma of the lung. Identification of a driver mutation, for which there is an available targeted therapy for treatments, results in better long-term survival for these patients. Multiplex testing is rapidly becoming the standard of care in patients with advanced stage adenocarcinoma of the lung and stage IV squamous cell carcinoma is likely to follow a similar clinical path.

Kris MG, Johnson BE, Berry LD et al: Using Multiplexed Assays of Oncogenic Drivers in Lung Cancer to Select Targeted Drugs; JAMA 2014; 311:1998-2006

A dedicated TOA reader asked about including squamous cell lung cancers in the Lung Cancer Mutation Trial. Dr. Jett replied, The study on molecular testing of squamous cell lung cancer is called the Lung MAP trial (SWOG 1400) and is for patients with metastatic or stage 4 squamous cell lung cancer who have failed first line therapy. Click here to view the Lung MAP study.