The EGFR inhibitor osimertinib may be an effective therapy for patients with untreated non–small cell lung cancer who have brain metastases. In a recent study, the drug extended median progression-free survival and increased objective response rates compared with the first-generation EGFR inhibitors gefitinib and erlotinib.
The EGFR inhibitor osimertinib (Tagrisso; AstraZeneca), often used as first-line treatment for patients with EGFR-mutated non–small cell lung cancer (NSCLC), may also be effective at treating brain metastases stemming from the disease. In a recent study, patients with untreated NSCLC and brain metastases who received the drug had better central nervous system (CNS) responses—including longer median progression-free survival (PFS) and higher objective response rates (ORR)—than patients who received a first-generation EGFR inhibitor, such as gefitinib (Iressa; AstraZeneca) or erlotinib (Tarceva; Genentech and Astellas).
Previously published results from the phase III FLAURA trial established that patients with EGFR-mutated NSCLC treated with osimertinib had longer median PFS and fewer side effects than those who received gefitinib or erlotinib, which led to FDA approval of the drug as a first-line therapy in April. However, Johan Vansteenkiste, MD, PhD, of the University Hospitals KU Leuven in Belgium, an author on both studies, notes that many patients—up to 40%—who receive EGFR inhibitors develop brain metastases, in part because the drugs extend overall survival. Thus, “it was of interest to see if there would be superiority of osimertinib over standard EGFR inhibitors in control and prevention of brain disease.”
Vansteenkiste and his team analyzed data from a subset of 200 patients in the FLAURA trial who had undergone serial brain scans, focusing on 128 patients with CNS lesions. They found that patients treated with osimertinib did not reach median PFS in the CNS, compared with a median CNS PFS of 13.9 months in those who received gefitinib or erlotinib.
Although 20% of patients treated with osimertinib had worsening CNS metastases, and 12% developed new lesions, patients who received gefitinib or erlotinib fared worse—39% and 30%, respectively. Additionally, osimertinib was associated with ORRs of 66% in patients with a CNS lesion of any size and 91% in those with at least one lesion larger than 10 mm, compared with ORRs of 43% and 68%, respectively, in patients who received one of the first-generation drugs.
Zofia Piotrowska, MD, of Massachusetts General Hospital Cancer Center in Boston, who was not involved in the study, says that although previous research on osimertinib indicated that it may be more clinically active in the CNS than older EGFR inhibitors, “those comparisons hadn't been done head to head, so to have these data is really important and clinically meaningful.”
Piotrowska would now like to know if the drug helps protect patients from developing brain metastases, as well as whether patients whose disease worsens on osimertinib should continue taking it as they begin receiving other therapies.
Pasi A. Jänne, MD, PhD, of the Dana-Farber Cancer Institute in Boston, MA, who was also not connected to the research, says that although many clinicians in the United States already use osimertinib in the first-line setting, the new findings provide “another reason to use it as a first-line therapy, because you have the ability not only to control the systemic disease better, but also to control the brain disease.”
Because so few drugs cross the blood–brain barrier, clinicians often treat brain metastases with radiation therapy, which can cause severe and lasting side effects. “Having a drug that can also treat the brain metastases is really a game-changer clinically,” he says. –Catherine Caruso