An individual patient-level meta-analysis of non–small-cell lung cancer leptomeningeal metastases treated with epidermal growth factor receptor inhibitors.

person David Jiahua Bian McGill University, Montreal, QC, Canada info_outline David Jiahua Bian, Anna-Maria Lazaratos, Sarah M. Maritan, Andrea Quaiattini, Zhimin Zeng, Zhengfei Zhu, Ugur Sener, Rachna Malani, Yu Jung Kim, Eiki Ichihara, Nathaniel Bouganim, Matthew Dankner

Authors person David Jiahua Bian McGill University, Montreal, QC, Canada info_outline David Jiahua Bian, Anna-Maria Lazaratos, Sarah M. Maritan, Andrea Quaiattini, Zhimin Zeng, Zhengfei Zhu, Ugur Sener, Rachna Malani, Yu Jung Kim, Eiki Ichihara, Nathaniel Bouganim, Matthew Dankner Organizations McGill University, Montreal, QC, Canada, Department of Oncology, the second affiliated hospital of Nanchang University, Nanchang, Jiangxi, China, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, Shanghai, China, Mayo Clinic, Rochester, MN, Memorial Sloan Kettering Cancer Center, New York, NY, Department of Internal Medicine, Division of Hematology and Medical Oncology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-Si, South Korea, OKAYAMA UNIVERSITY, Okayama-Shi Kita-Ku, Japan, McGill University Health Centre, Montreal, QC, Canada, McGill University, Montréal, QC, Canada Abstract Disclosures Research Funding No funding received None. Background: Leptomeningeal metastasis (LM) is a debilitating condition associated with advanced non-small cell lung cancer (NSCLC). When driver mutations in the epidermal growth factor receptor (EGFR) are identified, targeted therapies (TT) represent an appealing therapeutic strategy. However, the efficacy of TT for LM is unknown as LM patients are routinely omitted from clinical trials. Methods: We conducted a systematic review and meta-analysis of individual patient data to evaluate the efficacy of EGFR TT in EGFR-mutant NSCLC LM in accordance with PRISMA guidelines. EGFR-TTs evaluated were erlotinib, gefitinib, icotinib, afatinib, dacomitinib, osimertinib, zorifertinib, and furmonertinib. The co-primary endpoints were progression-free survival (PFS) and overall survival (OS). To assess differences between groups, shared frailty Cox regression models were used to estimate the hazard ratio (HR), 95% confidence interval (CI) and p-value. Results: 7780 abstracts were screened, identifying 126 publications with 232 patients, corresponding to 272 lines of EGFR-TT for NSCLC LM which met inclusion criteria. The overall median PFS (mPFS) in patients receiving any EGFR-TT was 9.15 months and the median overall survival was 14.5 months. In univariable analyses, osimertinib was associated prolonged PFS compared to other EGFR-TT, (mPFS of 11 versus 8 months, HR = 0.64; 95% CI: 0.44-0.93; P = 0.02). Osimertinib was numerically associated with prolonged OS compared to other EGFR-TT (mOS 16.8 months versus 13.6 months, HR = 0.72; 95% CI 0.44-1.17, P = 0.188). In multivariable analyses, ECOG performance status > 2 was independently associated with shortened PFS (mPFS 10 versus 8 months, HR = 1.54, 95% CI: 1.26-3.04; P < 0.05) and OS (mOS 16.5 versus 10 months, HR = 3.33, 95% CI: 1.80-6.18; P < 0.05). Conclusions: In the largest cohort of NSCLC LM treated with EGFR TT compiled to date, osimertinib is associated with marginally improved outcomes compared to other EGFR TTs. ECOG performance status is an independent predictor of prognosis in these patients. These results highlight the need for prospective studies for this difficult to treat patient population.