LBA69 Aumolertinib plus apatinib versus aumolertinib as first-line treatment in patients with EGFR mutation positive locally advanced or metastatic non-small cell lung cancer (NSCLC): A randomized multicenter study

The standard first-line treatment for locally advanced or metastatic EGFR-mutated NSCLC patients (pts) is the third-generation EGFR-TKI alone, which has limitations. Combining EGFR-TKI with a small molecule anti-angiogenic agent may be a potential solution due to synergistic effects. The ATTENTION study aims to evaluate the efficacy and safety of aumolertinib plus apatinib (AUM + APA) versus aumolertinib (AUM) alone as the first-line therapy for EGFR-mutated NSCLC. Eligible pts were aged 18-75 years old, stage IIIB or IV NSCLC, with EGFR 19del or 21L858R mutation or EGFR uncommon mutations, ECOG PS of 0 or 1, measurable lesion according to RECIST v1.1. We randomly assigned eligible pts in a 1:1 ratio to receive oral aumolertinib (110 mg PO QD) or adding apatinib (250 mg PO QD) until assessed progressive disease (PD). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), intracranial ORR (iORR), intracranial DCR (iDCR), overall survival (OS) and safety. From Jun. 2021 to Nov. 2022, a total of 104 pts were enrolled, 98 included in the efficacy analysis set. Of these, 48 pts received AUM + APA, while 50 pts received AUM. As of Sep. 12, 2023, the overall ORR was 72.9% and 64%, DCR was 100% and 94% in AUM + APA and AUM arms, respectively. In EGFR sensitizing mutation (19 del or L858R) subgroup, ORR was 75% and 68% in AUM + APA and AUM arms, respectively. In brain and liver metastasis subgroup, ORR were 100% and 60%, 60% and 33%, iORR was 82% and 63% in AUM + APA and AUM arms. PFS has beneficial trend in AUM + APA arm. The most common treatment-emergent adverse events (TEAEs) in AUM + APA and AUM arms were diarrhea (31% vs 12%), rash (29% vs 10%), proteinuria (27% vs 6%), platelet count decreased (25% vs 4%), hypertension (25% vs 6%), creatine kinase increase (23% vs 16%), respectively. The combination of AUM + APA may provide a more effective and well tolerable treatment option for the first line treatment in EGFR mutated NSCLC patients.