Abstract 683P
Background
EGFR-mutant NSCLC patients with brain metastasis show worse efficacy and prognosis. Aumolertinib proved to have better intracranial efficacy. Aumolertinib plus anlotinib possibly exhibit anti-tumor synergetic effect via diverse mechanisms. Herein, we conducted a prospective, phase II clinical study to explore the intracranial efficacy of aumolertinib plus anlotinib for NSCLC with brain metastasis. The prior results were reported and we had updated data.
Methods
Treatment-naïve EGFR-positive NSCLC patients with brain metastases were enrolled. All patients were orally administered aumolertinib (110mg daily) plus anlotinib (10 or 12mg according to BSA, daily on days 1-14, every 3 weeks). The primary endpoint was iPFS. Secondary endpoints included iORR, iDCR, PFS, OS and QoL.
Results
75 patients were recruited at data cut-off (May, 2024) with median follow-up time of 9.2 months (range 2.6-33.4). The median age was 60 years (range 28-75) and female accounted for 54.7%. 74(98.7%) patients harbored 19del (50.7%) or L858R mutation (48.0%). 24 patients developed encephaledema. 67 patients were evaluated intracranially with overall ORR 79.1% (95%CI: 67.4-88.1) and DCR 98.5% (95%CI: 92.0-100). The median PFS was 15.9 months (95%CI: 9.2-22.6) but median iPFS was not reached. The iORR was 77.6% (95%CI: 65.8-86.9) and iDCR was 100% (95%CI: 94.6-100). Wherein, the iORR for patients with oligometastasis or multiple brain metastases was 70.0% (95%CI: 34.8-93.3) and 78.9% (95%CI: 66.1-88.6). The iORR for patients with encephaledema was 90.5% (95%CI: 69.6-98.8). The iORR for 19del or L858R group was 88.6% (95%CI:73.3-96.8) and 64.5% (95%CI:45.4-80.8). NGS was tested in 49 patients. For TP53 comutation, iORR was 79.2% (95%CI:57.8-92.9). The commonest adverse event was Grade1/2 hypertension(22.7%).
Conclusions
Aumolertinib plus anlotinib displayed satisfactory outcome as first-line therapy in EGFR-mutant NSCLC patients with brain metastases regardless of the quantity of brain lesions and may demonstrated superior efficacy in patients with encephaledema or 19del positive. Patients with TP53 comutation can still benefit from combined therapy. Enrollment will continue for further analyses.
Clinical trial identification
NCT04978753; 07/10/2021.
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.