The combination of bevacizumab with atezolizumab plus chemotherapy can significantly improve the progression-free survival of metastatic non-small cell lung cancer patients with low serum VEGF-A levels.
A recent study published in Nature Communications highlights a breakthrough in lung cancer treatment, revealing that serum levels of vascular endothelial growth factor A (VEGF-A) can serve as a predictive biomarker for patient responses to therapies involving bevacizumab, atezolizumab, and platinum chemotherapy. This research, conducted as part of the APPLE study, illustrates the importance of measuring baseline concentrations of VEGF-A in patients with metastatic, nonsquamous non-small cell lung cancer (NSCLC) to better tailor treatment strategies.
The APPLE study, a randomized phase 3 trial, was conducted between January 2019 and August 2020, involving 412 patients who were administered either a combination of carboplatin, pemetrexed, and atezolizumab, or the same regimen with the addition of bevacizumab. The specific aim of this trial was to explore the efficacy of this combination therapy and identify predictive biomarkers that could help oncologists determine which patients could benefit most from the addition of bevacizumab.
In their preplanned analysis, researchers investigated the correlation between serum levels of VEGF-A and its isoforms, VEGF121 and VEGF165, with treatment responses. They employed an enzyme-linked immunosorbent assay (ELISA) to measure these levels before treatment began. The study revealed compelling results: patients with low baseline levels of VEGF-A displayed significantly improved progression-free survival (PFS) when treated with bevacizumab.
Notably, the median values for total VEGF-A (tVEGF-A) were found to be 405 pg/mL in the chemotherapy plus atezolizumab (Chemo/Atezo) group and 353 pg/mL in the bevacizumab combination group (Chemo/Atezo/Bev). Further analysis indicated that for those with low levels of tVEGF-A, VEGF121, or VEGF165, individuals in the Chemo/Atezo group experienced a shorter PFS compared to those in the Chemo/Atezo/Bev group—demonstrating the significance of VEGF-A levels as predictive markers.
This study's implications are profound. “Measurement of serum VEGF-A or its isoforms may identify NSCLC patients who are likely to benefit from the addition of bevacizumab to immunotherapy,” wrote the authors of the article. The ease of measuring serum VEGF-A offers potential for routine application in clinical settings, paving the way for personalized treatment strategies in lung cancer.
Despite the positive outcomes associated with low VEGF-A levels, the study also highlighted a concerning trend among patients with high levels of VEGF-A. In these cases, the addition of bevacizumab appeared to have no substantial benefits, leading to the suspicion that high serum VEGF-A might contribute to a less favorable treatment response. “Our study identified a potential biomarker for prediction of which patients are likely to benefit from the addition of bevacizumab to platinum-based chemotherapy and a PD-1 pathway inhibitor for the treatment of individuals with metastatic nonsquamous NSCLC,” the authors emphasized.
As the fight against NSCLC progresses, this study could mark a significant step toward optimizing treatment protocols by implementing biomarkers to predict patient responses. The focus on individual serum biomarkers rather than a one-size-fits-all approach could enhance patient outcomes and improve therapeutic strategies. By confirming these findings in further clinical studies, researchers may one day achieve breakthroughs that reshape the treatment landscape for lung cancer.
In conclusion, the discovery that measuring serum VEGF-A and its isoforms may provide crucial insight into patient responses to treatment reinforces the significance of personalized medicine in oncology. As research continues in this field, future studies will be vital for validating these biomarkers and integrating them into clinical practice to enhance care for lung cancer patients.
