1332P - Efficacy and safety of gefitinib plus bevacizumab versus gefitinib monotherapy in patients with EGFR L858R mutant non-small cell lung cancer (NSCLC): A randomized, open-controlled, single-center trial

Background

Dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor pathways may be a potential therapeutic strategy for EGFR mutant NSCLC. This study was conducted to assess the efficacy and safety of gefitinib (Gef) plus bevacizumab (Bev) for EGFR L858R mutation-positive NSCLC.

Methods

80 patients were randomly assigned to receive either Gef at 250 mg/day alone (group G, n = 39）or with Bev at 7.5 mg/kg every 3 weeks (group GB, n = 41). The primary endpoints were safety and progression-free survival (PFS), and the secondary endpoint was objective response rate (ORR). Genomic biomarkers and resistance mechanism were investigated.

Results

There was a significant reduction in the risk for progression in the group GB compared with the group G (HR = 0.49) with the median PFS (mPFS) of 15.1 vs. 8.2 mon (P =0.0031). The ORR was significantly higher in group GB than in group G (90.2% vs. 59.0%, P = 0.005). Adverse events were similar between two groups (85.4% vs. 70.7%, P=0.27). ctDNA status at 43 days after treatment initiation (D43) was associated with PFS, which was longer in patients with ctDNA negative (-) at D43 than those with ctDNA positive (+) at D43 in both groups (17.0 vs. 12.2 mon, P=0.008 in group GB; 10.2 vs. 4.3 mon, P<0.001 in group G). In 67 patients with matched baseline (BS) and D43 plasma samples, patients were divided into three groups: BS ctDNA- and D43 ctDNA- for type A, BS ctDNA+ and D43 ctDNA- for type B, and BS ctDNA+ and D43 ctDNA+ for type C. In type B, ORR was significantly higher in the group GB than in group G (100% vs. 64.7%, P=0.008). Type B had a comparable PFS with type A, both significantly longer than type C in both groups (mPFS 19.1, 18.8 and 11.2 mon for type A, B and C, P=0.016 in group GB; 15.9, 10.2 and 4.7 mon for type A, B and C, P<0.001 in group G). Post-progression samples from the group G showed a trend toward to higher frequency of T790M mutations compared with the group GB (70.6% vs. 38.5%, P=0.13).

Conclusions

Combined therapy of gefitinib with bevacizumab exhibited a significant improvement in PFS in patients with EGFR L858R mutant NSCLC. The post-treatment ctDNA and dynamic change were potential biomarkers of efficacy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Beijing Health Alliance Charitable Foundation; Guangzhou Life Oasis Public Service Center.

Disclosure

All authors have declared no conflicts of interest.