Dual inhibition of EGFR, VEGF improves progression-free survival in NSCLC

Inhibiting the pathways of both epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) leads to significant improvements in progression-free survival (PFS) but more adverse events (AEs), results of a meta-analysis have shown.

A team of investigators performed a systematic review and meta-analysis of relevant randomized trials between 2000 and 2022 to examine the efficacy and toxicity of the combined treatment with EGFR tyrosine kinase inhibitors (TKIs) and VEGF blockade for patients with advanced nonsmall cell lung cancer (NSCLC) harbouring activating EGFR mutations compared to EGFR TKIs alone.

Overall survival (OS) and PFS were the primary endpoints, while secondary ones included objective response rate (ORR), disease control rate, and grade ≥3 AEs. The investigators used the generic inverse variance and the Mantel-Haenszel methods to meta-analyse the pooled hazard ratios (HRs) and odds ratios (ORs).

Eight trials, including a total of 1,528 patients, met the eligibility criteria. The combination treatment reduced the risk of disease progression by 37 percent (HR, 0.63, 95 percent confidence interval [CI], 0.56‒0.72) but had no added benefit on OS vs EGFR inhibition alone (HR, 0.90, 95 percent CI, 0.76‒1.05).

Notably, no significant between-group difference was observed in terms of ORR or disease control rate.

However, a significant increase in AEs was observed in the dual treatment arm (OR, 3.02, 95 percent CI, 1.71‒5.31). The most frequent AEs seen were proteinuria and hypertension.

“Mature OS data are needed along with results from more trials exploring this strategy with third-generation EGFR TKIs to strengthen these results,” the investigators said.