Many patients with non-small cell lung cancer (NSCLC) present with advanced disease, which is highly resistant to chemotherapy. Recently, the use of tumor histology and relevant molecular biomarkers in determining optimal treatment strategies has improved outcomes for some patients, yet a number of targeted therapies are not applicable to patients without driver mutations. In this interview with i3 Health, Jamie E. Chaft, MD, a medical oncologist at Memorial Sloan Kettering Cancer Center and an Assistant Professor at Weill Cornell Medical College, discusses the challenges of treating advanced NSCLC without driver mutations and the research developments that are most likely to help patients.
What led you to pursue research in NSCLC? How has the field sustained your interest?
Jamie E. Chaft, MD: I selected research in lung cancer when I found a phenomenal mentor. This interest has been sustained by the rapid pace of advances in lung cancer leading to personalized care for our patients.
What are the greatest challenges of treating patients with advanced NSCLC without driver mutations?
Dr. Chaft: In patients without driver mutations, our greatest challenge is identifying the right drug or drugs. Biomarkers for the use of immunotherapy are far behind those that identify actionable oncogenes. We have a lot more work to do to understand who will and will not benefit from immunotherapy and who would be better served by immuno-oncology (IO)–chemo combination therapy versus chemotherapy alone.
What are the most important new developments in the treatment of advanced NSCLC without driver mutations?
Dr. Chaft: Immunotherapy drugs targeting programmed cell death protein-1 (PD-1), programmed death ligand-1 (PD-L1), and now CTLA-4 have clearly been the greatest advance in the treatment of patients with lung cancer without actionable driver mutations, and perhaps also in a subset of those with mutations after failure of a targeted therapy. These drugs are well tolerated and have the chance of unprecedented durable response.
How do you believe that the treatment of advanced NSCLC will evolve in the future?
Dr. Chaft: Improving our predictive biomarkers to better understand who will and will not benefit from immunotherapy and/or who may need combination therapies is our greatest unmet need in advanced disease, as is understanding if and when we can stop drugs in responders, perhaps through the use of liquid biopsies in the future.
What advice can you give to community oncologists treating patients with advanced NSCLC without driver mutations?
Dr. Chaft: Care has changed for all of our patients, with and without actionable oncogene driver mutations. Understanding all available predictive biomarkers, including PD-L1 expression, is essential in helping to personalize the treatment choice for each individual patient with advanced NSCLC.
About Dr. Chaft
Jamie E. Chaft, MD, a medical oncologist, is an Associate Member of Memorial Sloan Kettering Cancer Center, an Assistant Professor in Medicine at Weill Cornell Medical College, and an Associate Attending Physician at Memorial Hospital for Cancer and Allied Diseases. In her clinical work, she specializes in NSCLC, including multimodality therapies and early-stage disease. She has been the principal investigator on numerous clinical trials for lung cancer therapies, including erlotinib, crizotinib, nivolumab, ipilimumab, durvalumab, afatinib, atezolizumab, tremelimumab, and others. She serves on the Eastern Cooperative Oncology Group (ECOG) Thoracic Core Committee, the American Society of Clinical Oncology (ASCO)'s Targeted Agent and Profiling Utilization Registry (TAPUR) Study committee, the ASCO Guideline committee for resectable NSCLC, and the International Association for the Study of Lung Cancer (IASLC) Lung Cancer Screening and Early Detection Committee.
For More Information
Dr. Chaft is the Chair of i3 Health's CME-approved visiting faculty meeting series, New Thinking, New Strategies in the Treatment of Advanced NSCLC Without Driver Mutations. Contact i3 Health to request a meeting if you are interested in hosting this free presentation at your institution.
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily represent those of i3 Health.