Intracranial efficacy and safety of furmonertinib 160 mg with or without anti-angiogenic agent in advanced NSCLC patients with BM/LM as salvage therapy

Abstract

Objectives: Central nervous system (CNS) metastases including brain metastases (BM) and leptomeningeal metastases (LM) are frequent in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC), and are correlated with poor outcomes. In this study, we evaluated the efficacy of single-agent furmonertinib 160 mg or combining with anti-angiogenic agent in NSCLC patients who had developed BM/LM progression from previous tyrosine kinase inhibior (TKI) treatment.

Methods: EGFR-mutated NSCLC patients who developed BM (the BM cohort) or LM progression (the LM cohort) were included, having received furmonertinib 160 mg daily as second-line or later treatment, with or without anti-angiogenic agents. The intracranial efficacy was evaluated by intracranial progression-free survival (iPFS).

Results: Totally 12 patients in the BM cohort and 16 patients in the LM cohort were included. Almost one half of patients in the BM cohort and a majority in the LM cohort had a poor physical status, with a Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥2. The administration of single-agent furmonertinib or combination treatment achieved a median iPFS of 3.6 months (95%CI 1.435-5.705) in the BM cohort, and 4.3 months (95%CI 2.094-6.486) in the LM cohort. Subgroup and univariate analysis has shown that a good ECOG-PS correlated with a favorable efficacy of furmonertinib in the BM cohort (median iPFS = 2.1 with ECOG-PS ≥ 2 vs. 14.6 months with ECOG-PS < 2, P < 0.05). Overall, any grade of adverse events (AEs) occured in 46.4% of patients (13/28). Among them, 14.3% of patients (4 of 28) had grade 3 or higher AEs, and were all under control, led to no dose reductions or suspension.

Conclusion: Single-agent furmonertinib 160 mg or in combination of anti-angiogenic agent is an optional salvage therapy for advanced NSCLC patients who developed BM/LM progression from prior EGFR-TKI treatment, with a promising efficacy and an acceptable safety profile, and is worth of further exploration.

Keywords: Anti-angiogenic agent; BM/LM; EGFR-mutated NSCLC; Furmonertinib; Salvage therapy.

Conflict of interest statement

The authors declare no competing interests.

© 2023. The Author(s).

Figures

Fig. 1

Survival analysis in the brain metastases (BM) and leptomeningeal metastases (LM) cohorts. A Median progression-free survival (PFS) and B intracranial PFS (iPFS) in the BM cohort. C Median PFS and median iPFS (D) in the LM cohort

Fig. 2

Survival analysis in each cohort with different characteristics and treatment strategies. Median intracranial progression-free survival (iPFS) in A the BM cohort, and B the LM cohort with different physical status. Median iPFS in C the BM cohort, and D the LM cohort who had treated with other third-generation TKI prior to furmonertinib or not. Median iPFS in E the BM cohort, and F the LM cohort treated with furmonertinib 160 mg monotherapy or in combination with anti-angiogenic agent

Fig. 3

Typical examples in (epidermal growth factor receptor) EGFR-mutant non-small cell lung cancer (NSCLC) patients successfully treated with furmonertinib 160 mg as salvage treatment who had intracranial progression to prior tyrosine kinase inhibior (TKI). A A female patient had extracranial progression along with newly-diagnosed brain metastases (BM) and leptomeningeal metastases (LM) after first-line chemotherapy and afatinib. A secondary genetic test has shown EGFR exon 19del mutation (73.8%), EGFR exon20 T790M mutation (28.7%), and EGFR amplification (CN = 11.9). The patients then received furmonertinib 160 mg combining with bevacizumab as second-line treatment, and had a significant improvement in dizziness which was related to her central nervous system (CNS) disease. The targeted lesion in her brain had a complete response (CR), and the metastatic cervical lymph nodes also had a partial response (PR). 1) Multiple lesions in brain after first-line treatment; 2) Complete response to furmonertinib; 3) Cervical lymphnodes after first-line treatment; 4) Partial response to furmonertinib. B A male patient diagnosed as advanced EGFR-mutant NSCLC with BM received afatinib as first-line treatment for 14 months, and had an intracranial progression and edema with severe CNS-related symptoms such as fatigue and vomiting. A gene detection at progression showed EGFR exon19 deletion mutation (1.36%) and TP53 mutation (0.85%), whereas no T790M mutation in circulating tumor DNA (ctDNA). The patient then received furmonertinib 160 mg and bevacizumab along with radiotherapy in CNS. The targeted lesion in her brain and the primary lesion in lungs had a PR, and her symptoms were significantly relieved. 1) Multiple lesions in brain after first-line treatment; 2) Partial response to furmonertinib; 3) Primary lesion in lung after first-line treatment; 4) Partial response to furmonertinib