Up Front NGS Among Top Advances in Lung Cancer

Azadeh Namakydoust, MD

One of the more recent advances in lung cancer treatment includes next-generation sequencing (NGS) upon diagnosis, which has provided guidance on the optimal treatment for each individual patient, explained Azadeh Namakydoust, MD.

“Many targetable mutations have been identified, and the pace of [mutation identification] is increasing as we do more molecular testing and NGS panels,” said Namakydoust. “It's important that all of our patients have one of these panels done for them—whatever may be available to them by their oncologists. It's crucial to [perform these panels] to decide on a treatment and have that [information] on hand, in case a patient needs a new treatment or progresses on first-line treatment.”

In an interview during the 2019 OncLive^® State of the Science Summit™ on Non—Small Lung Cancer, Namakydoust, a thoracic oncologist at Memorial Sloan Kettering Cancer Center, discussed recent advancements in lung cancer and what the future holds.

OncLive: What have been the key recent advances in lung cancer treatment?

Namakydoust: We have made tremendous progress even in the past 10 years, never mind the past 30 years. Certainly, there are traditional chemotherapy regimens that are still in use and effective. However, one of the most exciting and life-changing developments in lung cancer has been the emergence of immunotherapy as an integral part of the treatment plans that we offer patients.

In addition to immunotherapy, there are many targeted therapies that we are now able to offer our patients because we have been able to do NGS and molecular analysis of tumors, which allows us to offer more targeted and also effective treatments.

In terms of immunotherapy, for patients with stage IV disease for non—small cell lung cancer, we are moving towards the use of combining checkpoint inhibitors and chemotherapy for patients who have a high burden of disease or are very symptomatic from their malignancy. Another exciting area is seeing the use of durvalumab (Imfinzi) after chemotherapy and radiation, which has been practice changing in the past couple of years.

Additionally, in terms of targeted treatments, with more NGS panels using more targetable mutations, we have more therapies that we are able to develop. For example, at Memorial Sloan Kettering Cancer Center, [NGS] is standard of care for all patients diagnosed with NSCLC and most patients with small cell lung cancer (SCLC), regardless of stage, to receive our NGS impact panel to inform us of the mutations that are present in the patient's tumor. Hopefully, we can use them to individualize the treatments.

What is the status of chimeric antigen receptor (CAR) T-cell therapy in lung cancer treatment?

CAR T-cell therapy is mainly in the clinical trial setting, especially for mesothelioma. At Memorial Sloan Kettering Cancer Center, we have a very robust clinical trial program for several different solid tumors. As it relates to lung cancer and thoracic malignancies, mesothelioma is the main [disease state] that we are working on. We have several patients that I personally have put on our CAR T-cell therapy trial.

What targets are being examined in SCLC?

There are currently no targetable mutations in SCLC that are known, but there are a lot of data emerging. There is very interesting work that my service chief, Charles M. Rudin, MD, PhD, is doing. We are finding that there are mutations in SCLC, and hopefully we can use them in the future to develop targeted treatments for them.

What does the future of lung cancer treatment look like in the next 5 years?

Treatments are going to become more individualized. Even in terms of checkpoint inhibitors, we're trying to identify which patients will have these long-term, durable responses that we see in a small subset of the population. How do we deal with the adverse events (AEs) that we are seeing? As we're using these drugs more, we're learning more about their associated AEs and how to manage them.

Another question that I personally deal with in my practice is whether there is a safe time to stop checkpoint inhibitors after a patient has had a very good, durable response—sometimes for a number of years. There are a lot of emerging data and retrospective studies taking a look at that question. It's not [a question] that has been answered definitively.