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Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
A Phase I Trial of VEGF-A Inhibition Combined with PD-L1 Blockade for Recurrent Glioblastoma
Daniel Chiu1, Jingjing Qi2, Tin Htwe Thin3
1Icahn School of Medicine at Mount Sinai, New York, New York.
Purpose:
The treatment of glioblastoma (GBM) poses challenges. The use of immune checkpoint inhibition (ICI) has been disappointing as GBM is characterized by low mutational burden and low T-cell infiltration. The combination of ICI with other treatment modalities may improve efficacy.
Patient And Methods:
Patients with recurrent GBM were treated with avelumab, a human IgG1 antibody directed against PD-L1 (part A), or avelumab within a week after laser interstitial thermal therapy (LITT) and continuation of avelumab (part B). Bevacizumab was allowed to be combined with ICI to spare steroid use. The primary objective was to characterize the tolerability and safety of the regimens. The secondary objectives included overall survival, progression-free survival (PFS), signatures of plasma analytes, and immune cells.
Results:
A total of 12 patients (median age 64; range, 37-73) enrolled, five in part A and seven in part B. Two serious adverse events occurred in the same patient, LITT treated, not leading to death. The median survival from enrollment was 13 months [95% confidence interval (CI), 4-16 months] with no differences for part A or B. The median PFS was 3 months (95% CI, 1.5-4.5 months). The decrease in MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival.
Conclusions:
Avelumab was generally well tolerated. Adding bevacizumab to ICI may be beneficial by lowering cytokine and immune cell expression. The development of this combinatorial treatment warrants further investigation. Exploring the modulation of adaptive and innate immune cells and plasma analytes as biomarker signatures may instruct future studies in this dismal refractory disease.
Significance:
Our phase I of PD-L1 inhibition combined with LITT and using bevacizumab to spare steroids had a good safety profile for recurrent GBM. Developing combinatory treatment may help outcomes. In addition, we found significant immune modulation of cytokines and immune cells by bevacizumab, which may enhance the effect of ICI.
Insights
This study explored combining PD-L1 inhibition with laser interstitial thermal therapy and bevacizumab for recurrent glioblastoma. The combination showed a good safety profile and potential for improved outcomes in this challenging cancer.
Area of Science:
- Neuro-oncology
- Immunotherapy
- Cancer treatment
Background:
- Glioblastoma (GBM) treatment is challenging due to low mutational burden and T-cell infiltration, limiting immune checkpoint inhibition (ICI) efficacy.
- Combining ICI with other modalities may enhance treatment outcomes for GBM.
- Recurrent GBM presents a significant unmet medical need.
Purpose of the Study:
- To evaluate the safety and tolerability of combining PD-L1 inhibition (avelumab) with laser interstitial thermal therapy (LITT) and bevacizumab in recurrent GBM patients.
- To explore the impact of this combination on overall survival, progression-free survival (PFS), and immune biomarkers.
Main Methods:
- A Phase I clinical trial involving patients with recurrent GBM.
- Treatment arms included avelumab alone (Part A) or avelumab post-LITT (Part B), with bevacizumab allowed to reduce steroid use.
- Primary endpoints focused on safety and tolerability; secondary endpoints included survival and immune cell/cytokine signatures.
Main Results:
- The combination therapy, including avelumab with or without LITT and bevacizumab, demonstrated a generally good safety profile.
- Median overall survival was 13 months, and median PFS was 3 months.
- Decreased levels of MICA/MICB, γδT cells, and CD4+ T cell EMRA correlated with prolonged survival.
Conclusions:
- The combination of PD-L1 inhibition, LITT, and bevacizumab is a safe and potentially effective approach for recurrent GBM.
- Bevacizumab may enhance ICI efficacy by modulating cytokine and immune cell profiles.
- Further investigation into immune cell and plasma analyte modulation as biomarkers is warranted.
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