Genetic Testing Delivers Personalized Lung Cancer Therapy

Mark G. Kris, MD

Taking a page from breast cancer treatment, clinicians managing lung cancer patients can now detect mutations that drive the development of lung cancer and subsequently target them with specific drugs, according to research presented Saturday at the ASCO conference in Chicago.

“The ability to detect driver mutations like EGFR and EML4-ALKin tumor specimens from patients with lung cancer and administer agents targeting those molecular lesions has revolutionized the management of adenocarcinoma of the lung,” wrote 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 City, and colleagues. “The availability of multiplexed assays to detect mutations permits the identification of multiple driver mutations from tumors at diagnosis.”

In the prospective study, the 14-member Lung Cancer Mutation Consortium (LCMC) has identified at least 1 of 10 recognized “driver” mutations in tumors in nearly two-thirds of patients with advanced lung cancer, according to Kris. He believes that lung cancer patients will embrace genetic testing for treatment.

“For years, in truth, we’ve done this with breast cancer,” said Kris in an interview with OncLive.com editor Anita T. Shaffer. “The tumor tissue is tested for estrogen receptor/progesterone receptor and if you had it, you received tamoxifen or aromatase inhibitor; if you didn’t, you just didn’t receive it. I think patients very much accept this because they want the best treatment for them.”

The LCMC allows the member institutions to pool their testing expertise and techniques with one another, as well as share results and outcomes. According to the study’s authors, the LCMC is prospectively enrolling patients to test tumors from lung adenocarcinoma in Clinical Laboratory Improvement Amendments (CLIA) laboratories for KRAS, EGFR, HER2, BRAF, PIK3CA, AKT1, MEK1, and NRASusing standard multiplexed assays and fluorescence in situ hybridization (FISH) for anaplastic lymphoma kinase(ALK) rearrangements and MET amplifications.

The consortium has enrolled its first 1000 patients; in the first 830 patients, a driver mutation was detected in 60% of participants (252 of 422 tumors). This has provided the opportunity for treating physicians to tailor available treatments to individual patients, such as using the EGFR inhibitor drug erlotinib (Tarceva) for those patients expressing EGFR mutations.

The cost of genetic testing for the driver mutations is between $750 and $1250, said Kris. “Compared with a month’s worth of a cancer drug, it’s really a very small amount of money, and that information can be used forever,” he noted. “You have to put [it] in context of what we learn. The results of this test can tell you if a medicine has a 90% chance of helping you. Conversely, if you don’t have the mutation, it has a 1% chance of helping you. I think ultimately it saves costs because you’re not giving expensive drugs to people who are going to receive no benefit.”

Sonali Smith, MD, an associate professor of medicine at the Center for Advanced Medicine at the University of Chicago Medical Center, who moderated the press conference at which the study was presented, observed that the work of the LCMC can lead to better management and treatment of lung cancer.

“I think that what is very clear is that lung cancer is increasingly recognized as being more than just one disease,” she said. “Having a rapid panel such as this to help guide therapy is very, very promising. Hopefully, this will encourage clinical trial participation and facilitate the development of other agents that are very targeted for this disease.”

Kris MG, Johnson BE, Kwiatkowski AJ, et al. Identification of driver mutations in tumor specimens from 1000 patient with lung adenocarcinoma: the NCI’s Lung Cancer Mutation Consortium (LCMC). J Clin Oncol. 29:2011(suppl; abstract CRA7506).