378P - Could the model of EGFR-TKIs plus antiangiogenesis as first-line treatments in patients with EGFR-mutated non-small cell lung cancer take a step further: A updated meta-analysis

Background

EGFR-TKIs are standard care for advanced NSCLC patients with EGFR mutation and are inevitably developed to acquired resistance. The addition of antiangiogenesis to first-generation EGFR-TKIs was a promising treatment strategy due to significantly improved PFS. However, OS benefit wasn’t observed. It remains unclear whether this combination strategy could move further.

Methods

RCTs and meeting abstracts investigated EGFR-TKIs plus antiangiogenesis as 1 line setting or osimertinib plus antiangiogenesis as the 2 line treatment on progression of first or second generation EGFR-TKIs treatment for NSCLC patients were systematically searched in relevant databases. The main outcomes measures included PFS, OS, ORR, AEs, and the incidence of acquired T790M mutation after 1 line EGFR-TKIs plus antiangiogenesis treatment. Fixed effects and random effects models were used to estimate pooled hazard ratios and relative risks.

Results

6 studies involving 1537 patients were included to assess the combination of EGFR-TKIs and antiangiogenesis as 1 line care in advanced NSCLC with EGFR mutation and results showed the approach significantly improved PFS (HR 0.62, 95%CI 0.54-0.70) compared EGFR-TKIs alone, especially in patients with L858A mutation (HR 0.64, 95%CI 0.54-0.76). However, OS (HR 0.95, 95%CI 0.78-1.15), ORR (HR 1.04, 95%CI 0.98-1.10), and the frequency of acquired T790M mutation (HR 0.88, 95%CI 0.73-1.07) showed no significant difference between 2 groups. 2 studies with 236 patients were pooled to evaluate osimertinib plus bevacizumab as the 2 line setting in patients with EGFR and T790M mutation and results showed the strategy was failed to improve PFS (HR 0.96, 95%CI 0.68-1.37), OS (HR 0.96, 95%CI 0.68-1.37) and ORR (HR 1.07, 95%CI 0.84-1.36). Risks of grade 3-5 AEs was increased in combination group (HR 1.68, 95% CI 1.52-1.86).

Conclusions

EGFR-TKIs plus antiangiogenesis as 1 line setting significantly prolonged PFS in patients with EGFR-positive NSCLC, particularly in patients with the L858R mutation, but was failed to improve OS. The addition of bevacizumab to osimertinib as 2 line treatment was unable to improve the efficacy of osimertinb in PFS, OS and ORR.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Gansu Provincial Cancer Hospital.

Funding

1. The Special Project for Major Disease Prevention and Treatment of Administration of Traditional Chinese Medicine in Gansu Province (grant number GZKZD-2018-03) 2. The Health Industry Scientific Research Program of Gansu Province in 2019 (grant number GSWSKY-2019-82), 3. The Science and Technology Development Guiding Program of Lanzhou City of Gansu Province (grant number 2019-ZD-134).

Disclosure

All authors have declared no conflicts of interest.