Osimertinib a Potential Treatment Option for Intracranial Metastatic Disease

Study findings support the use of osimertinib in the management of patients with intracranial metastatic disease (IMD; JAMA Netw Open. 2020;3[3]:e201617).

“Targeted therapy may address the limitations of current treatments as an additional agent to achieve intracranial disease control in some patients with IMD. Given the paucity of evidence regarding effectiveness, current guidelines have not made recommendations on the use of targeted therapy,” said Anders W. Erickson, BS, Student, Institute of Medical Science, Faculty of Medicine, University of Toronto, Ontario, Canada, and colleagues.

“Osimertinib mesylate is a mutant [EGFR] inhibitor that can penetrate the blood-brain barrier and inhibit tumor cell survival and proliferation in patients with non–small cell lung cancer (NSCLC) with specific EGFR alterations,” they continued.

Thus, using data from published studies reporting the intracranial outcomes of patients with metastatic EGFR-variant NSCLC and IMD treated with osimertinib, Mr Erickson et al evaluated the safety and efficacy of the inhibitor in this patient population.

Overall, 15 studies selected from MEDLINE and Embase databases and reporting on 324 patients fulfilled eligibility criteria for inclusion in the meta-analysis. Data from these studies (eg, study characteristics, intracranial effectiveness measures, and safety measures) were pooled via a random-effects model, with risk for bias evaluated using the Cochrane risk for bias tool and modified Newcastle-Ottawa Scale.

“Meta-analyses of proportions were conducted to pool estimates for central nervous system (CNS) objective response rate and CNS disease control rate,” Mr Erickson and co-investigators said.

Ultimately, the CNS objective response rate and disease control rate were 64% (95% CI, 53%-76%; n = 195) and 90% (95% CI, 85%-93%; n = 246), respectively. In addition, complete intracranial response rates were reported as between 7% and 23%; median best decrease in intracranial lesion size was −40% to −64%; and rates of grade ≥3 adverse events were 19% to 39%.

There were no additional sources of heterogeneity found in the subgroup analyses.

“Findings reported herein support a potential role for osimertinib in the treatment of patients with metastatic EGFR-variant NSCLC and IMD treated with osimertinib,” Mr Erickson and colleagues said.

“Clinical decision makers would benefit from the inclusion of patients with IMD in future trials to identify factors that predict responses to targeted therapy,” they concluded. —Hina Porcelli