Researchers Provide Updates on Benefits of Bevacizumab in NSCLC

Next week, researchers from around the globe will gather in Geneva, Switzerland, for the 2019 European Lung Cancer Congress. During the meeting, multiple research teams will discuss new findings from research into the use of bevacizumab—which now has approved biosimilars that promise cost savings and expanded patient access—in nonsquamous non—small-cell lung cancer (NSCLC).

First, a research team will report on an investigation of the immune-modulatory effects of a regimen of paclitaxel, carboplatin, and bevacizumab in patients with advanced NSCLC.¹ In this study, 223 patients were enrolled to receive the chemotherapy regimen with bevacizumab. Patients’ peripheral blood was assessed at baseline and after the first and second treatment cycles for the proportion of T cells, B cells, and monocytes.

The investigators found that, 6 weeks after starting treatment, the proportion of T cells was significantly increased relative to baseline. Within subsets of T cells, CD4 T cells remained stable, while proliferation of Ki67—positive CD8 T cells was significantly increased. These CD8 T cells express more programmed death receptor 1 (PD-1) compared with nonproliferating CD8 T cells.

The researchers concluded that the chemotherapy regimen plus bevacizumab induced the proliferation of more cells expressing coinhibitory checkpoint molecules; while progression-free survival (PFS) and overall survival were not impacted by this increase on its own, these findings do show a rational for using the regimen together with checkpoint inhibition.

However, another research team will report that previous use of bevacizumab is linked with inferior benefits from PD-1 and programmed death ligand 1 (PD-L1) inhibitors in NSCLC.²

In this study, researchers identified 133 patients who had been treated with PD-1/PD-L1 inhibitors, and 14.2% of them had previous bevacizumab treatment for NSCLC. Patients who had previous exposure to bevacizumab had shorter PFS than those who had no previous exposure (1.9 months vs 4.3 months, P  = .017), and the researchers concluded that prior bevacizumab use indicated poorer benefits from anti—PD-1/PD-L1 agents.

Finally, a research team will report on its findings that adding bevacizumab to an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) prolongs survival in patients with NSCLC with multiple brain metastases.³

In their study, the investigators studied 164 patients, each with more than 3 brain metastases, 121 of whom received EGFR-TKI as a first treatment and 43 of whom received EGFR-TKI plus bevacizumab. The response rate was marginally higher in bevacizumab group than that in monotherapy group (69.7% vs 52.9%, P&thinsp; = .055). Inclusion of bevacizumab was associated with a significantly longer intracranial PFS (13.5 months vs 7.3 months, P&thinsp; <.001) and systemic PFS (14.4 months vs 8.8 months, P &thinsp;<.001) than monotherapy. Median OS was also longer in the bevacizumab group than the monotherapy group (30.1 months vs 22.4 months, P &thinsp;<.001).

The researchers say that the strategy of adding bevacizumab to EGFR-TKI should be explored in a large-scale clinical trial as a standard treatment in this clinical setting.

References

1. Dumoulin D, De Goeje P, Poncin M, et al. Paclitaxel/ carboplatin/ bevacizumab in non-small cell lung cancer patients induces peripheral effector CD8 T cell proliferation that could be prone for treatment with checkpoint inhibitors. Presented at the 2019 European Lung Cancer Congress; April 10-13, 2019; Geneva, Switzerland. Abstract 22P.

2. Zhou F, Pan Y, Zhou C. Previous exposure to bevacizumab indicated inferior benefits from PD-1/PD-L1 inhibitors in nonsquamous NSCLC . Presented at the 2019 European Lung Cancer Congress; April 10-13, 2019; Geneva, Switzerland. Abstract 171P.

3. Jiang T, Zhou C. EGFR-TKIs plus bevacizumab demonstrated survival benefit than EGFR-TKIs alone in EGFR-mutant NSCLC patients with multiple brain metastases. Presented at the 2019 European Lung Cancer Congress; April 10-13, 2019; Geneva, Switzerland. Abstract 189O.