P116 Real World Data of 1st Line A+T in Advanced EGFR+ NSCLC: Clinical Outcome, PFS Influential Factors and Acquired Resistance

The PFS advantage of bevacizumab combined to EGFR-TKI (A+T) over EGFR-TKI monotherapy in 1st line treatment of advanced EGFR mutant NSCLC was firstly reported in phase 2 randomized trial JO255671 and newly demonstrated in phase 3 randomized trial NEJ0262. However, this combination had not been evaluated in the real world, the influential factor of PFS was not sure, and we knew little about the acquired resistance which is of great importance to the subsequent therapy, thus we conducted this study to address these medical needs. A total of 30 advanced EGFR mutant (Del19/L858R) NSCLC patients who received Bevacizumab plus Erlotinib/Gefitinib from March 2014 to July 2017 in Hunan Cancer Hospital were enrolled in this analysis. Clinical information was fully collected. NGS (Burrning rock biotech, 168 genes panel) was applied to detect genetic aberration in both tissue and blood samples, in a dynamic pattern: tissue test before treatment and at progression; blood analysis before treatment, at first radiography evaluation, at the last radiography evaluation before progression and at progression. All patients benefited from this combination. The overall response rate (ORR) was 77% and the median progression survival m(PFS) was 16 months. Neither baseline brain metastasis nor concomitant TP53 mutation shortened PFS (with vs without, 16 m vs 16 m, p=0.79; 17m vs 13m, p=0.34). Of EGFR mutation analysis by NGS, the concordant rate was well enough, 70% (21/30) between the paired initial tissue and blood samples. At progression, T790M was defined as the domain acquired resistance mechanism, contributing 43.8%, followed by MET amplification (12.5%), ERBB2 amplification (6.3%), high abundance of SMAD4 mutation (6.3%). Subgroup analysis showed patients with SMAD4 mutation have shorter PFS compared with those without SMAD4 mutation (10m vs 16m, p=0.035), while EGFR amplification did not impact PFS (17m vs 16m, p=0.60). The efficacy of A+T combination was encouraging in the clinical practice and the PFS data 16m in the overall population is consistent with what observed in clinical trials. Patients with baseline brain metastasis & concomitant TP53 and EGFR amplification at progression benefited similar in PFS compared to those without these characters. T790M and MET amplification are the domain acquired resistance mechanism. SMAD4 mutation was regarded as novel resistance mechanism, with PFS shorter than 1 year. We will do a continuous observation on A+T combination in the real world. Reference 1, KATO T, et al. 2014 ASCO Abstract 8005#. 2, Furuya N, et al. 2018 ASCO Abstract 9006#.