Abstract 75P
Background
Third-generation EGFR-TKIs are the preferred first-line treatment for EGFR-mutated non-small cell lung cancer (NSCLC). But EGFR-TKIs exhibit suboptimal treatment outcomes in NSCLC with EGFR L858R mutation compared with EGFR exon 19 deletion. Firmonertinib (AST2818) is an oral, brain-penetrant third-generation EGFR TKI with a wide therapeutic range and minimal toxicity. Anlotinib is an oral multitargeted tyrosine kinase inhibitor for tumor angiogenesis. Here, we investigated the efficacy and safety of firmonertinib plus anlotinib as first-line treatment for advanced EGFR L858R mutated NSCLC.
Methods
This ongoing study is a prospective multicenter phase II trial, planning to enroll 35 untreated advanced NSCLC patients with EGFR L858R mutation. The regimen consisted of firmonertinib (80 mg qd) and anlotinib (12 mg qd, day 1 to 14 every 21-days /cycle). The primary endpoint is objective response rate (ORR). Secondary endpoints include progression-free survival (PFS), disease control rate (DCR), safety, patient-reported outcomes (PRO), etc. The prognostic impact of ctDNA status after 3 weeks of treatment will be exploratively evaluated in this study.
Results
As of the data cut-off on January 10, 2025, 16 patients were enrolled and received study treatment. The baseline characteristics included median age 59 years (range 39–73), female 50%, stage IV adenocarcinoma (100%). 11 patients underwent at least one efficacy evaluation. Median follow-up was 255 days and the median PFS was not yet reached. The ORR assessed by investigator based on RECIST 1.1 was 90.9%, DCR was 100%. Median Depth of response (DpR) was 41.1%. Grade≥3 TRAEs were experienced by 1 (9.1%) patient. The most common adverse reactions were hemoptysis, epistaxis, hoarseness and rash. The ctDNA clearance occurred in 4 patients after 3 weeks of treatment. Higher tumor shrinkage was observed among these 4 patients, with the DpR being 79.4%, 67.5%, 46.3%, 45.9%, respectively.
Conclusions
This study demonstrated that firmonertinib plus anlotinib as first-line treatment for advanced EGFR L858R mutant NSCLC had an encouraging efficacy and well tolerated safety profile. Long-term follow up for this study is ongoing to further explore additional survival outcomes.
Clinical trial identification
ChiCTR2300072027.
Legal entity responsible for the study
The authors.
Funding
Beijing Xisike Clinical Oncology Research Foundation.
Disclosure
All authors have declared no conflicts of interest.