567P - Furmonertinib in combination with bevacizumab and intrathecal chemotherapy as later-line re-challenge treatment in EGFR –mutated NSCLC patients with leptomeningeal metastasis after third-generation EGFR-TKIs treatment failure

Background

Leptomeningeal metastasis (LM) is one of the most severe complications of non-small cell lung cancer (NSCLC) and is always accompanied by poor prognosis. The optimal treatment for EGFR–mutated NSCLC patients with LM after EGFR-TKI therapy failure remains unclear. Furmonertinib is a novel third-generation EGFR-TKI. A phase I-II dose-expansion study (NCT03127449) suggested that furmonertinib had a favorable antitumor activity with a wide therapeutic range and minimal toxicity. This retrospective study aimed to evaluate the efficacy and safety of furmonertinib 160mg in combination with bevacizumab and intrathecal chemotherapy in EGFR-mutated NSCLC patients with LM after initial TKI failure in the real world.

Methods

We retrospectively studied 19 NSCLC pts with LM treated with furmonertinib in combination with bevacizumab and intrathecal chemotherapy between February 2021 and April 2023 at Nanjing Chest Hospital. All of them received third-generation EGFR TKIs-based therapies previously. Objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), and toxicity were assessed.

Results

The median age was 57 years (range: 31-77), 6 (31.6%) were males and 13 (68.4%) were females. 4 (21.1%) had EOCG 2, 7 (36.8%) had ECOG 3, and 8 (42.1%) had ECOG 4. 16 patients (84.2%) had partial remission (PR) of LM lesions, 3 patients (15.8%) had stable disease (SD). The intracranial ORR (iORR) was 84.2% and intracranial DCR (iDCR) was 100%. 5 patients achieved PR and 14 patients had SD in the whole lesion, ORR was 26.3% and DCR was 100%. Median PFS was 11.9 months (95% CI 2.8–21.0). The overall survival data were not mature (the overall maturity was 26%). Treatment-related adverse events of ≥ grade 3 occurred in only 1 (5.3%) of 19 patients. Safety profile consistent with previous studies of furmonertinib.

Conclusions

Rechallenges of furmonertinib in combination with bevacizumab and intrathecal chemotherapy has shown significant efficacy and tolerable safety profile in EGFR–mutated NSCLC patients with LM after third-generation EGFR-TKIs treatment failure. The further exploration is ongoing.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.