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Despite Success With Targeted Therapies in NSCLC, Drug Resistance Remains Issue

Caroline Seymour
Published: Wednesday, Dec 12, 2018

Stephen L. Graziano, MD

Stephen L. Graziano, MD

Targeted therapies are extending progression-free survival (PFS) and overall survival (OS) in patients with oncogene-driven non–small cell lung cancer (NSCLC), although they are not curative agents, said Stephen L. Graziano, MD.

State of the Science Summit™ on Advanced Non–Small Cell Lung Cancer, Graziano discussed available and emerging targeted therapies for common driver mutations in patients with NSCLC and the sequencing strategies beyond frontline treatment.

OncLive: What are the available targeted therapies for patients with EGFR and ALK abnormalities?

Graziano: Targeted therapy is becoming established as the standard of care in most oncology practices. When a patient is diagnosed with adenocarcinoma of the lung, it’s standard practice to do at least a limited panel of markers that include EGFR, ALK, ROS1, and BRAF. We’re testing for PD-L1, as well. Generally, we do the panel so that we can choose initial therapy for the patient. If patients are positive for EGFR mutations— either deletion 19 or exon 21—we generally will start with osimertinib as the first-line therapy; that has been established based on data in recent publications.

mutations, it’s double oral therapy with dabrafenib (Tafinlar) and trametinib (Mekinist), which is similar to how we treat [patients with] melanoma.

Are there any particularly compelling data for patients with these alterations?

For EGFR, osimertinib has been established as the drug of choice for first-line therapy, but it may be a little controversial. A general principle in oncology is to use your best drug first. Most oncologists would go right to osimertinib. If the patient progresses after osimertinib, then the next line of therapy is similar to that of other patients: chemotherapy with or without immunotherapy.

Are any new agents on the horizon for these targets?

New agents are coming [through the pipeline] every month or so. Lorlatinib was just approved by the FDA for ALK-positive patients. Second-line drugs for ALK-positive patients include ceritinib, alectinib, brigatinib, and lorlatinib—so there are many options.
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Online CME Activities
TitleExpiration DateCME Credits
Oncology Briefings™: Individualizing Treatment After Second-Line Therapy for Patients With mCRCAug 29, 20191.0
Community Practice Connections™: Immunotherapeutic Strategies with the Potential to Transform Treatment for Genitourinary CancersAug 29, 20191.0
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