Osimertinib May Be Beneficial for NSCLC Patients With Intracranial Metastasis

By Marilynn Larkin

April 03, 2020

NEW YORK (Reuters Health) - Results of a systematic review and meta-analysis support a possible role for osimertinib in the management of non-small-cell lung cancer (NSCLC) patients with intracranial metastatic disease, researchers say.

"The development of metastatic disease to the brain is a common and serious complication of lung cancer," Dr. Sunit Das of St. Michael's Hospital and University of Toronto, Canada, told Reuters Health by email. "Historically, these tumors have required treatment with surgery or radiation."

However, the team's current work suggests that some patients - those with epidermal growth factor receptor (EGFR)-variant disease and brain metastases - can be treated medically, with the mutant EGFR inhibitor osimertinib.

As reported in JAMA Network Open, Dr. Das and colleagues searched the literature and identified 15 studies reporting intracranial outcomes for 324 patients with metastatic EGF-R-variant NSCLC and intracranial metastatic disease treated with osimertinib.

"We found that...64% experienced a measurable response, and 90% experienced disease control in the central nervous system with osimertinib therapy," Dr. Das said.

Included studies reported complete intracranial response rates of 7% to 23%; a median best decrease in intracranial lesion size of 40% to 64%; and grade 3 or higher adverse event rates of 19% to 39%. No additional sources of heterogeneity were found in subgroup analyses.

Dr. Das said, "These findings support a potential role for osimertinib in the treatment of patients with intracranial metastatic disease secondary to EGFR-mutant lung cancer, and suggest that we may be able to treat these patients without concerns associated with surgery and radiation therapy."

However, he added, "The drug is only effective in patients with EGFR-mutant disease, which only accounts for about 15% of patients with lung cancer."

Dr. Stephanie Weiss, Chief, Neurologic Oncology at Fox Chase Cancer Center in Philadelphia, commented in an email to Reuters Health, "While this study suggests that select patients with brain metastases from osimertinib-sensitive lung cancers may able to forgo upfront radiotherapy, this strategy should be approached with caution."

"Radiosurgery has superior one-year local control and a favorable side effect profile," she noted. "Earlier data suggest that survival of similar patients with brain metastases is superior with radiation added to tyrosine kinase inhibitor drugs; however, osimertinib was not included in that study."

"This analysis cannot answer whether or not this observation holds for this drug," she said.

"Decision making should therefore always involve a multidisciplinary team including a radiation oncologist so that the risk-benefit profile can be individualized for patients, and they can be followed appropriately so as not to lose the effective window of opportunity for successful treatment with radiation," Dr. Weiss concluded.

SOURCE: https://bit.ly/347xFhL JAMA Network Open, online March 25, 2020.

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