Lung Cancer Pioneer Thomas Lynch Discusses the State of the Art

Thomas Lynch, MD

Thomas Lynch, MD, has been a leader in the development of numerous novel therapies for the treatment of lung cancer. His significant contributions to the field have earned him great recognition, including the 2013 Giants of Cancer CareTM award in Lung Cancer for his pioneering use of molecular testing for EGFR mutations.

Lynch, who is director of the Yale Cancer Center and physician-in-chief at the Smilow Cancer Hospital at Yale-New Haven, recently sat down with OncLive and discussed key strategies and trends in the management of lung cancer. In a wide-ranging interview, Lynch provides expert insight across the spectrum of care, from screening to the challenges associated with resistance mutations.

OncLive: What impact do you think Medicare’s decision to cover CT screening for lung cancer will have on prevention and treatment?

Dr Lynch: The Medicare decision to broaden coverage to include CT scans is very important for our patients. CT scans have been shown to reduce the risk of lung cancer by 20%, which is not trivial. I am a big fan of this update. I think the greatest impact it will have is increasing cure. Patients who will now be diagnosed with surgically curable disease would not have had the same diagnosis, in the past.

Of course, not all patients will be curable. In some patients, the CT scan will pick up widely metastatic disease. There will also be some instances where a screening test will reveal abnormalities that turn out not to be cancer, and the patient will have a lot of anxiety over something that is not serious.

How do treatment strategies differ for patients with non—small cell lung cancer with and without detected mutations?

There is a lot of emphasis on finding targeted therapies in lung cancer. However, there is a big group of patients who don’t have identifiable oncocytic drivers and treating them is equally important. You need to know if you are dealing with EGFR, ALK, ROS or wild-type.

If it is wild-type, then it is important to think about what role antiangiogenic therapy could play. Should you use drugs like bevacizumab or ramucirumab in the treatment of this disease?

You should also decide if this is a group of patients that is appropriate for referral to a clinical trial. There are some populations where bevacizumab plus chemotherapy might be a great approach, and others where chemotherapy alone might be the right way to go.

At this point, we believe that approximately 18% of patients with non—small cell lung cancer have disease that is molecularly targetable with specific inhibitors. However, that doesn’t mean that only 18% of lung cancer has disease that is driven by oncogene addiction. There are going to be more subsets that we will find. The difficult thing is that they are not going to be easy subsets; they are not going to be big groups of patients. They are going to be 1% to 2% of the overall percentage pie. RAF and RAS mutations drive a lot of lung cancers. However, we don’t have active treatments that work terribly well against them, but we do know that they are oncogene driven and it is our job to come up with better treatments to address that.

How do new treatment options in the second-line setting affect your first-line treatment decisions?

New treatment options in second-line expand the number of choices an oncologist has. In oncology, and in lung cancer in particular, we really want to use our best drugs first. Plus, you want to use the drugs that will give the patient the best chance of survival and the best chance of response.

What second-line choices do is simply expand the number of effective options that doctors have in this setting. We are excited that, in many types of lung cancer, we now have effective second-line and third-line therapies. Drugs such as ramucirumab may offer an opportunity to expand options for second-line therapy.

What do you think of the recent advances in squamous cell lung cancer?

The squamous population looks very exciting. This looks like it might be a group of patients who may broadly benefit from immunotherapy and from a group of antibodies, such as nimotuzumab. This group of patients has not really benefited from treatment advances up until now. I am excited to see what the data will show for treatment options for patients with squamous cell lung cancer.

How do you suggest approaching the management of T790M resistance mutations?

Monitoring and looking for T790M is important, both when someone is newly diagnosed and as treatment emerges down the road when patients become resistant. Repeat biopsies make a huge difference. Dr Scott Gettinger and Dr Katie Politi, my colleagues at Yale, have published extensively on the role that second biopsies can play in driving treatment decisions.

If you know you have T790M, it opens up a whole new class of drugs, such as AZD9291 and others that look like they have activity in patients with T790M.