1350P - Survival benefits of local treatment (LT) for brain metastases (BMs) in patients (pts) with EGFR-mutant non-small cell lung cancer (EGFR-mt NSCLC) treated with osimertinib

Background

Osimertinib is a standard treatment for pts with EGFR-mt NSCLC and is highly effective for BMs. It is unclear whether upfront LT for BMs prolong survival of pts with EGFR-mt NSCLC. The aim of this study was to reveal the survival benefit of upfront LT for BMs in pts with EGFR-mt NSCLC treated with osimertinib.

Methods

We conducted a multicenter (9 centers in Japan), retrospective cohort study of consecutive pts with EGFR-mt NSCLC who had BMs before the initiation of osimertinib between August 2018 and October 2021. Pts with meningitis were excluded. We divided all pts into two groups: pts who received upfront LT for BMs followed by osimertinib (Upfront LT group) and pts who received osimertinib without upfront LT (Osimertinib alone group). Overall survival (OS) and central nervous system progression free survival (CNS-PFS) between the two groups were compared. Inverse probability treatment weighting (IPTW) analysis with propensity scores was performed to adjust for potential confounding factors.

Results

A total of 121 pts was enrolled: median (range) age 72 (40–89) years; 83 (69%) female; 92 (76%) ECOG PS 0–1, 29 (24%) PS 2–4; 116 (96%) adenocarcinoma; EGFR status 57 (47%) 19del, 64 (53%) L858R; number of BMs 37 (31%) single, 84 (69%) multiple; median (range) maximum size of BMs 10 (1–51) mm; Symptoms of BMs 26 (21%) yes, 95 (79%) no; 45 (37%) upfront LT, 76 (63%) osimertinib alone. IPTW-adjusted Kaplan-Meier curves showed that OS of pts in the upfront LT group was significantly longer than that of pts in osimertinib alone group (median, Not reached (NR); 95% CI, NR–NR versus median, 31.2 months; 95%CI, 21.7–33.2; p=0.021). IPTW-adjusted HR for OS was 0.37 (95%CI, 0.16–0.87). IPTW-adjusted HR for CNS-PFS was 0.36 (95%CI, 0.15–0.87).

Conclusions

These results suggest that upfront LT for BMs followed by osimertinib may improve survival for pts with EGFR-mt NSCLC despite the high CNS activity of osimertinib.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

T. Tozuka: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Chugai Pharmaceutical Co., Ltd., AstraZeneca K.K.. R. Noro: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Chugai Pharmaceutical, AstraZeneca, Merck Pharmaceutical, Pfizer Pharmaceutical, Meijiseika Pharmaceutical, GSK Pharmaceutical, Daiichi Sankyo Pharmaceutical; Financial Interests, Personal and Institutional, Funding: the Promotion of Joint International Research (Fostering Joint International Research), and Grant-in-Aid for Scientific Research (C). T. Hakozaki: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Chugai Pharmaceutical, Eisai, Ono Pharmaceutical. T. Naito: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca. Y. Hosomi: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Eli Lilly Japan, Taiho Pharmaceutical, Chugai Pharmaceutical, Ono Pharmaceutical, Bristol Myers Squibb, Kyowa Kirin , Nippon Kayaku, Takeda, Eisai , Novartis, Pfizer. T. Hirose: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca K.K.. T. Okano: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd. AstraZeneca K.K. Bristol Myers Squibb K.K. Eli Lilly Japan K.K. Takeda Pharmaceutical Co., Ltd, Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., AstraZeneca K.K., Bristol Myers Squibb K.K., Eli Lilly Japan K.K., Takeda Pharmaceutical Co., Ltd; Financial Interests, Personal, Expert Testimony: Pharmaceuticals and Medical Devices Agency. M. Seike: Financial Interests, Personal and Institutional, Other, Grants or contracts from any entity: Taiho Pharmaceutical, Chugai Pharmaceutical, Eli Lilly, Nippon Boehringer Ingelheim, Nippon Kayaku, Kyowa Hakko Kirin; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, MSD K.K, Chugai Pharmaceutical, Taiho Pharmaceutical, Eli Lilly, Ono Pharmaceutical, Bristol Myers Squibb, Nippon Boehringer Ingelheim, Pfizer, Novartis, Takeda Pharmaceutical, Kyowa Hakko Kirin, Nippon Kayaku, Daiichi Sankyo Company, Merck Biopharma, Amgen inc. All other authors have declared no conflicts of interest.