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The Efficacy and Safety of Adding Teniposide to Temozolomide Plus Bevacizumab in Recurrent Grade 4 Glioma: A Real-World Exploratory Single-Center Study

Year: 2026

Type: article

Abstract: Background: Salvage options for recurrent grade 4 glioma (GBM) remain limited and no single standard of care has been established after recurrence. Teniposide (VM-26) has been reintroduced into clinical practice, but its benefit when added to temozolomide (TMZ) plus bevacizumab (Bev) in recurrent grade 4 glioma remains unclear. Methods: This single-center, real-world exploratory study retrospectively enrolled 53 patients with recurrent grade 4 glioma who received either teniposide plus TMZ and Bev (VM26 + TMZ + Bev, n = 26) or TMZ plus Bev (TMZ + Bev, n = 27). The control group combined patients treated before teniposide became available again in China (2020–2022) with those treated concurrently with the triplet (2023–2026). Safety was assessed using the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0; tumor response was evaluated according to the Response Assessment in Neuro-Oncology (RANO) criteria on an intention-to-treat basis, and survival was estimated by the Kaplan–Meier method. Results: Median progression-free survival (PFS) was 7.8 months (95% confidence interval (CI), 4.9–10.9) in the VM26 + TMZ + Bev group versus 5.1 months (95% CI, 4.4–6.8) in the TMZ + Bev group (log-rank p = 0.037; unadjusted hazard ratio (HR) 0.50, 95% CI, 0.25–0.97), and median overall survival (OS) was 12.7 months (95% CI, 8.4–15.4) versus 8.5 months (95% CI, 7.3–9.7) (log-rank p = 0.042; unadjusted HR 0.47, 95% CI, 0.23–0.98). Multivariable adjustment strengthened these estimates, whereas propensity score weighting and matching gave estimates of the same direction that did not reach significance. The objective response rate (ORR) was 26.9% (7/26) versus 14.8% (4/27) (p = 0.327) and the disease control rate (DCR) was 80.8% versus 77.8% (p = 1.000). Grade ≥ 3 adverse events (AEs) occurred in 11.5% versus 7.4% of patients (p = 0.669); leukopenia and neutropenia were more frequent with teniposide (26.9% vs. 3.7%; p = 0.024) but lost significance after Benjamini–Hochberg correction (q = 0.122). No unexpected toxicity types were observed, although any-grade leukopenia and neutropenia were more frequent with teniposide and should be anticipated in clinical use. Conclusions: In this exploratory real-world cohort, adding teniposide to TMZ plus Bev was associated with longer PFS and OS and a numerically higher ORR, without a significant increase in grade ≥ 3 toxicity, although any-grade leukopenia and neutropenia were more frequent and should be anticipated; however, treatment era could not be fully separated from treatment effect: in an era-matched analysis restricted to the concurrently treated cohorts, the direction of the effect was preserved but did not reach significance. The survival differences rested on a small number of events and were not robust to reclassification of individual patient outcomes. These findings warrant confirmation in prospective randomized studies.

Source: Journal of Clinical Medicine

DOI: 10.3390/jcm15207827