PD-1 inhibition has only limited clinical benefit in patients with recurrent high-grade glioma

Abstract

Objective: To investigate the question of whether salvage therapy with the programmed cell death protein 1 (PD-1)-blocking antibodies nivolumab or pembrolizumab with or without bevacizumab offers clinical or survival benefit in patients with recurrent high-grade gliomas (HGGs).

Methods: This was a single-institution retrospective observational study in 31 adult patients who received pembrolizumab (Keytruda) or nivolumab (Opdivo) with or without concurrent bevacizumab for recurrent high-grade glioma.

Results: Median progression-free survival (mPFS) from first anti-PD-1 dose was 3.2 months (95% confidence interval [CI] 2.2-4.2), and there was no difference in patients receiving nivolumab (mPFS 3.8 months, 95% CI 1.7-5.8) compared to patients receiving pembrolizumab (mPFS 2.3 months, 95% CI 1.7-2.8, log rank 3.1, p = 0.08). There was also no difference in mPFS if patients had previously received bevacizumab (mPFS 3.2 months, 95% CI 2-4.3) or were bevacizumab naive (mPFS 3.7, 95% CI 0-7.9, log rank 1.3, p = 0.3). The median survival from date of first anti-PD-1 dose was 6.6 months (95% CI 4.2-9.1).

Conclusion: Salvage therapy with nivolumab or pembrolizumab with or without bevacizumab does not confer a survival benefit in this heavily pretreated unselected patient population. Until the results of the currently ongoing clinical trials become available, the use of PD-1-blocking antibodies should be considered in selected individuals only.

Classification of evidence: This retrospective observational study provides Class IV evidence that for patients with recurrent HGGs, salvage therapy with nivolumab or pembrolizumab does not significantly improve survival.