Thomas J. Lynch, MD, CEO, chairman, Massachusetts General Hospital Physicians Organization, 2013 Giant of Cancer Care: Lung Cancer, discusses targeting 

 mutation subtypes as a frontline treatment for lung cancer.

Over the years, researchers have learned that the unique sensitivity in lung cancer with tyrosine kinase inhibitors (TKIs) is driven by the presence of 

 mutations. A common challenge faced by oncologists, Lynch explains, is how to treat patients based on the individual mutations that are discovered through molecular testing.

Most mutation subtypes, such as exon 19 and exon 20, are relatively common, Lynch explains. However, 11% of patients have more uncommon mutations, which can be challenging to treat. Common 

 mutations are targeted with therapies such as gefitinib, afatinib, and erlotinib, and researchers are investigating if these agents can also be used to treat the less common drivers. Not all of these mutations confer sensitivity to TKIs, Lynch adds.

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Thomas J. Lynch, MD, CEO, chairman, Massachusetts General Hospital Physicians Organization, discusses targeting EGFR mutation subtypes as a frontline treatment for lung cancer.

Dr. Lynch on Targeting EGFR Mutation Subtypes in Lung Cancer

Thomas J. Lynch, MD, director, Yale Cancer Center, physician-in-chief, Smilow Cancer Hospital at Yale-New Haven, Giant of Lung Cancer Care, discusses expanding the number of molecular subsets in non-small cell lung cancer (NSCLC).

Approximately 18% of patients with NSCLC have disease that is molecularly targetable with specific inhibitors. However, Lynch explains this does not mean the same population has disease that is solely driven by oncogene addiction, and that there are more subsets researchers hope to find.

The difficult part of this expansion process is knowing the subsets will not be found in large groups of patients, while 

 mutations are often discovered in NSCLC cases. Lynch adds that treatments are not available to accurately target these other subsets, but a starting point is knowing they are oncogene-driven.

Dr. Lynch on Expanding Molecular Subsets in NSCLC

Thomas J. Lynch, MD, director, Yale Cancer Center, physician-in-chief, Smilow Cancer Hospital at Yale-New Haven, Giant of Lung Cancer Care, explains how resistance occurs when treating patients with lung cancer using EGFR TKIs.

Lynch says that while EGFR TKIs help patients with 

-mutated lung cancer, the vast majority of these patients will develop resistance. Half of the time, resistance is caused by the 

 mutation, Lynch says. The other instances of resistance are caused by other factors, such as amplification of the 

 gene, or mutations or amplification of the 

This variation in the resistance mechanism warrants rebiopsy for patient who develop resistance to frontline therapy, Lynch notes. Biopsying a patient after resistance can help physicians decide which agent to give their patient next. Novel next-generation EGFR inhibitors are being developed that are targeted against the 

 acquired mutation. These therapies, AZD9291 and rociletinib (CO-1686), have demonstrated response rates near 60% in clinical trials.

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Thomas J. Lynch, MD, from the Yale Cancer Center, explains how resistance occurs when treating lung cancer patients with EGFR TKIs.

Dr. Lynch Discusses Resistance to EGFR TKIs in Lung Cancer

Thomas J. Lynch, MD, Richard Sackler and Jonathan Sackler Professor of Medicine (Medical Oncology), director, Yale Cancer Center, physician-in-chief, Smilow Cancer Hospital at Yale-New Haven, Giant of Lung Cancer Care, discusses advances in molecular profiling in lung cancer.

Lynch says physicians have learned to molecularly profile non-small cell lung cancer (NSCLC) and can now find an actionable mutation in 40-45% of patients.

As more is learned about mutations, more agents are being developed. There are now second- and third-generation EGFR inhibitors that could have greater efficacy than some older-generation drugs, Lynch says. New second-generation ALK inhibitors and ROS1 inhibitors are also showing promise.

The range of actionable mutations in NSCLC continues to increase, Lynch says, and physicians are now able to find an agent to interact with the specific mutation of the patient.

Dr. Lynch on Molecular Profiling in Lung Cancer

Thomas J. Lynch, Jr., MD, from the Yale Cancer Center, pioneered the use of molecular testing for EGFR mutations in lung cancer. In July 2013, he was honored by OncLive as one of the "Giants of Cancer Care."

The 2013 Giants of Cancer Care was conducted at the Hyatt Regency in Huntington Beach, California.

For more information on the Giants of Cancer Care, visit 

Thomas J. Lynch, Jr., MD

Articles

Dr. Lynch on Targeting EGFR Mutation Subtypes in Lung Cancer

Dr. Lynch on Expanding Molecular Subsets in NSCLC

Dr. Lynch Discusses Resistance to EGFR TKIs in Lung Cancer

Dr. Lynch on Molecular Profiling in Lung Cancer

Dr. Lynch Accepts His 'Giants of Cancer Care' Award