KEY TAKEAWAYS
- The phase II clinical study investigated the intracranial efficacy of combining aumolertinib with anlotinib in treating NSCLC patients with brain metastasis.
- The study’s primary endpoint was iPFS. Secondary endpoints were iORR, iDCR, PFS, OS, and QoL.
- The initial findings suggest that aumolertinib with anlotinib is an effective first-line treatment for NSCLC patients with EGFR mutations and brain metastases.
This phase II clinical study enrolled treatment-naïve, EGFR-positive NSCLC patients (pts) with brain metastases, including those with ≥ 3 brain lesions and those with 1-2 lesions who were either not candidates for or were unwilling to undergo local treatment. All pts were administered aumolertinib (110mg, orally QD) in conjunction with anlotinib (12mg for those with a BSA of ≥1.6 m2 and 10mg for those with a BSA of <1.6 m2, orally QD, day 1 to 14 of a 21-day cycle).
Treatment continued until disease progression or the emergence of intolerable toxicity. The primary objective was intracranial Progression-Free Survival (iPFS). Secondary objectives included intracranial Overall Response Rate (iORR), intracranial Disease Control Rate (iDCR), Progression-Free Survival (PFS), Overall Survival (OS), and Quality of Life (QoL).
As of the cut-off date on March 28, 2023, 40 pts participated in the study, 39 of whom were evaluable intracranially. The median follow-up period averaged 8.8 months (ranging from 3.0 to 30.2 months). The median age of the pts was 61 years and 22 of them were female. The iORR and iDCR were 74.4% (29 out of 39 pts; 95% Confidence Interval [CI]: 57.9-87.0) and 100% (39 out of 39 pts; 95%CI: 91.0-100), respectively.
The median depth of tumor remission (DepOR) for intracranial lesions stood at 42.86%. Specifically, the iORR was 77.4% (24 out of 31 pts; 95%CI: 58.90-90.41) for those with multiple brain metastases and 62.5% (5 out of 8 pts; 95%CI: 24.5-91.5) for those with oligometastasis. When categorized by gene type, the iORR was 88.9% (16 out of 18 pts; 95%CI: 65.3-98.6) in the 19del group and 61.9% (13 out of 21 pts; 95%CI: 38.4-81.9) in the 21L858R group.
Next-Generation Sequencing (NGS) was performed on 27 pts. In the comutation group, which included TP53, EGFR amplification, MET amplification, PIK3CA, and CCND1 amplification among others, the iORR was 74.1% (20 out of 27 pts; 95%CI: 53.7-88.9). For the subgroup with TP53 comutation, the iORR was 77.8% (14 out of 18 pts; 95%CI: 52.4-93.6). The median PFS was not determined yet.
The combination of aumolertinib and anlotinib showed initial efficacy as a first-line treatment for NSCLC pts with EGFR mutations and brain metastases. The early data from subgroups suggested that this treatment combination may be particularly effective in pts with multiple intracranial metastases or EGFR 19Del positive. The study’s enrollment is ongoing, and further analysis will be conducted.
Source: https://cattendee.abstractsonline.com/meeting/10925/presentation/997
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT05778149
Chen, L.K., Chen, J., Li, M.C., Yu, H., Zhang, B.S., Hou, X. Aumolertinib Plus Anlotinib in Advanced NSCLC with Brain Metastasis: A Single-arm, Phase II Study.
