New lung cancer consortium identifying tumour 'driver' mutations in advanced cancer to improve treatment choice

The ability to detect mutations that drive the development of lung cancer and subsequently target them with specific drugs has changed the management of the disease.

In a prospective study, the 14-member Lung Cancer Mutation Consortium (LCMC) has identified at least one of 10 recognized "driver" mutations in tumours in nearly two-thirds of patients with advanced lung cancer.

Investigators suggest that the LCMC program is an important model for care and research, showing that patients' tumours may be analyzed for mutations at diagnosis in a systematic way, and data can be given to physicians to help guide care of that patient to use available targeted therapies or encourage participation in clinical trials.

"Over the past decade, it's become clear that adenocarcinoma of the lung – the most common type of lung cancer – is defined by types of DNA damage in the tumour. While identifying the specific mutations can inform treatment decisions and improve outcomes, many centers have not routinely done this because of a lack of funding and available testing technology for mutations," said lead author Mark G. Kris, MD, chief of the Thoracic Oncology Service and The William and Joy Ruane Chair in Thoracic Oncology at Memorial Sloan-Kettering Cancer Center in New York. "The idea behind the consortium was to create a lasting process at each institution to routinely obtain information on tumour mutations and use it to choose the most appropriate therapy for each patient. It's a proof of concept that individual institutions can do this routinely at diagnosis."

The LCMC has already enrolled more than 1,000 patients with advanced (stage IIIB/IV) lung cancer to test lung adenocarcinoma tumours for 10 recognized driver mutations in genes, including KRAS, EGFR, HER2, BRAF, PIK3CA, AKT1, MEK1, and NRAS, and for ALK rearrangements and MET amplifications.

In the first 830 patients, a driver mutation was detected in 60 percent of participants (252 of 422 tumours). For some patients, such as those with EGFR mutations, treating physicians use the results to select the EGFR inhibitor drug erlotinib (Tarceva) as initial treatment. Drugs such as trastuzumab (Herceptin) and lapatinib (Tykerb) target HER2, and the agent crizotinib is now undergoing U.S. Food and Drug Administration review for use in the 8,000 patients with lung cancer found each year to carry mutations in the ALK gene. Patients with other types of driver mutations are offered participation in trials given through the LCMC institutions that test agents aimed at the particular mutations identified.

As a result of the LCMC program, such "multiplex testing" for many tumour mutations at once is now routine at many of the LCMC sites. According to Dr. Kris, while the lung cancer consortium focuses on patients with advanced lung cancer, some cancer centers already routinely analyze tumours for mutations soon after surgery. He said the same process can be used for other subtypes of lung cancer, and is applicable for other cancers. Oncologists treating patients with colorectal cancer being considered for treatment with cetuximab or panitumumab routinely analyze tumour specimens for the KRAS gene.

Source: ASCO

Reference: ASCO 2011 Abstract: CRA7506: Identification of driver mutations in tumour specimens from 1000 patients with lung adenocarcinoma: The NCI's lung cancer mutation consortium (LCMC). M. G. Kris, B. E. Johnson, D. J. Kwiatkowski, A. J. Iafrate, I. I. Wistuba, S. L. Aronson, J. A. Engelman, Y. Shyr, F. R. Khuri, C. M. Rudin, E. B. Garon, W. Pao, J. H. Schiller, E. B. Haura, K. Shirai, G. Giaccone, L. D. Berry, K. Kugler, J. D. Minna, P. A. Bunn.