15P Furmonertinib combined with anlotinib as the first-line treatment in patients with EGFR exon 21 Leu858Arg mutation: Results from FOCUS-A study

Furmonertinib is a novel third-generation EGFR-TKI with high brain penetration, wide therapeutic range and minimal toxicity. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor for tumor angiogenesis. There is limited data of third-generation TKI combined with anlotinib in the naïve patients with EGFR-mutated NSCLC. For the L858R population, associated with a worse prognosis, combining a third-generation TKI with an anti-angiogenic drug could offer a potential strategy to enhance efficacy in this population. FOCUS-A study is a prospective multicenter phase II trial, enrolled 40 patients who were locally advanced or metastatic NSCLC with EGFR-sensitive mutations. Patients with stable brain metastasis can be enrolled. The regimen is consisting of furmonertinib (80mg, qd) and anlotinib (10 mg qd, day 1 to 14 every 21-days /cycle). The primary endpoint is objective response rate (ORR). The secondary endpoints include progression-free survival (PFS), Disease Control Rate (DCR), Duration of Response (DOR), safety, etc. Until Data Cut-Off 2023.12.21, 40 patients have been fully enrolled, with 22 of them having the L858R mutation. For L858R subgroup, efficacy were all completed with at least 2 time assessment and median follow-up was 13.96 months. The baseline characteristics were as follows: the median age was 62.5 years (range 50-71), female (63.6%), never smokers (86.4%), stage IV adenocarcinoma (90.9%) and CNS metastases (36.4%). The ORR was 95.45%(95%CI, 77.2-99.9)assessed by the investigator with RECIST1.1 criteria, with 21 patients achieved partial response (PR) and 1 patient stable disease (SD), DCR was 100%. Median Depth of response (DpR) was 42.0%. Grade≥3 TRAEs were experienced by 5 (22.7%) patients the most common adverse reactions were hypertension and elevation of creatinine. The follow-up remains ongoing. FOCUS-A study demonstrated that furmonertinib plus anlotinib as first-line treatment for advanced EGFR L858R mutant NSCLC had an outstanding efficacy with manageable safety.