Serum VEGF-A as a biomarker for the addition of bevacizumab to chemo-immunotherapy in metastatic NSCLC.

Summary

In a preplanned biomarker analysis within a phase 3 trial (APPLE), baseline serum VEGF-A (and isoforms) measured by ELISA identified metastatic nonsquamous NSCLC patients who derived significant PFS benefit from adding bevacizumab to atezolizumab plus platinum chemotherapy. The work supports serum VEGF-A as a practical predictive biomarker for tailoring anti-VEGF use with chemo-immunotherapy.

Key Findings

• Baseline low serum VEGF-A identified patients with significant PFS benefit from adding bevacizumab to atezolizumab + platinum chemotherapy.
• VEGF-A and its isoforms can be quantified via ELISA, enabling practical implementation.
• Preplanned analysis within a phase 3 RCT supports VEGF-A as a predictive (not merely prognostic) biomarker for anti-VEGF add-on.

Clinical Implications

Consider baseline serum VEGF-A testing to guide adding bevacizumab to atezolizumab plus platinum chemotherapy; patients with low VEGF-A appear to gain PFS benefit. Validation and cutoff standardization are needed before routine adoption.

Limitations

• Biomarker groups were not randomized; potential residual confounding
• Findings derived from a single trial dataset without external validation or prespecified universal cutoffs

Future Directions

Conduct prospective biomarker-enriched or biomarker-stratified RCTs, define and validate universal VEGF-A/isoform cutoffs, and assess cost-effectiveness and OS benefit.