The treatment of advanced-stage non-small cell lung cancer (NSCLC) has improved steadily in the past few years, and individualized therapy for patients with mutations in the epidermal growth factor receptor (EGFR) is applied in routine clinical practice. While EGFR-mutated NSCLC is effectively treated with tyrosine kinase inhibitors (TKIs) such as erlotinib or gefitinib, there is a need to develop more effective treatments to improve outcomes in these patients. In a study now published in The New England Journal of Medicine, a team of researchers led by Suresh S. Ramalingam, MD, the Deputy Director of Winship Cancer Institute at Emory University, reported that osimertinib, an EGFR TKI, significantly increased both progression-free survival and overall survival in patients with EGFR-mutated NSCLC. In this interview with i3 Health, Dr. Ramalingam discusses the benefits of osimertinib and the future of treatment for patients with this disease.
What are some of the most challenging aspects of treating patients with EGFR-mutated advanced NSCLC?
Suresh S. Ramalingam, MD: Approximately 15% to 35% of lung adenocarcinomas have EGFR mutations. For these patients, EGFR TKIs are the preferred therapy. With the first- and second-generation agents, however, acquired resistance through activation of the T790M pathway is a major clinical problem. These agents also have relatively limited activity against brain metastases.
Can you comment on the significance of your results regarding osimertinib for EGFR-mutated advanced NSCLC?
Dr. Ramalingam: In the FLAURA study, osimertinib showed significant improvement in both progression-free survival and overall survival compared with erlotinib or gefitinib. This is the first trial to demonstrate an improvement in survival as compared with another TKI. Osimertinib was tolerated well and had robust activity against brain metastases. These benefits represent a major step forward in the treatment of EGFR-mutated lung cancer.
How do you see the treatment of EGFR-mutated NSCLC evolving?
Dr. Ramalingam: Osimertinib has now emerged as the preferred first line of therapy for patients with an EGFR mutation. As we continue to understand the mechanisms of resistance to first-line osimertinib, novel combination approaches that delay or overcome resistance are already being undertaken. Osimertinib is also being studied in stage I, II, and III NSCLC in efforts to improve cure rates.
Do you have any words of advice for community oncologists treating patients with EGFR-mutated advanced NSCLC?
Dr. Ramalingam: Molecular testing is critical in order to guide therapy for lung adenocarcinoma, and it is important to wait for the results before treatment is initiated. If a patient's clinical situation demands the initiation of some form of therapy before molecular testing is completed, chemotherapy alone is the recommended approach. Initiation of immunotherapy for this group of patients could potentially result in serious adverse events if patients are subsequently switched to TKI therapy. Additionally, TKI therapy is the preferred approach for patients with EGFR-mutated NSCLC regardless of programmed death-ligand 1 (PD-L1) expression.
About Dr. Ramalingam
Suresh S. Ramalingam, MD, is a Professor of Hematology and Medical Oncology, Director of the Division of Medical Oncology, and Assistant Dean of Cancer Research at Emory University School of Medicine in Atlanta, Georgia. He serves as the Deputy Director of Emory's Winship Cancer Institute, where he is also Director of the Lung Cancer Program. In addition, he is the President of the Georgia Society of Oncology. Dr. Ramalingam specializes in the treatment of lung cancer, and his research focuses on the development of immune checkpoint inhibitors and novel therapeutic options to improve outcomes in patients with EGFR-mutated NSCLC.
For More Information
Ramalingam SS, Vansteenkiste J, Planchard D, et al (2019). Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC. N Engl J Med. [Epub ahead of print] DOI:10.1056/NEJMoa1913662
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily represent those of i3 Health.