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Journal Club

Tumor/Skull Base

Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma.

J Clin Oncol | 2009

Rapid review note

Journal Club is a rapid, AI-assisted appraisal layer. It highlights study design, effect estimates, and practice relevance, but it is still a briefing, not a replacement for the paper.

For education only. Not medical advice.

Paper snapshot

Rapid study overview

Open paper

DOI

10.1200/JCO.2008.16.3055

PMID

19114704

PICO

Population

Adult patients with recurrent glioblastoma after radiotherapy and temozolomide.

Intervention

Single-agent bevacizumab 10 mg/kg every 2 weeks.

Comparator

Historical controls (PFS6 9% from prior studies).

Outcomes

6-month progression-free survival (PFS6), radiographic response, overall survival, toxicity.

Design

Type

Single-arm phase II trial.

Randomized

No

Multicenter

No

Blinded

Not applicable: open-label single-arm design.

Follow-up

Assessments every 4 weeks with MRI.

Primary endpoint

PFS6 (progression-free survival at 6 months).

Secondary endpoints

  • Radiographic response rates (Levin and Macdonald criteria)
  • Overall survival
  • Toxicity assessment

Practice impact

What this means

This phase II trial of single-agent bevacizumab in 48 recurrent GBM patients showed 29% PFS6 and median PFS of 16 weeks, with 71% radiographic response by Levin criteria. Toxicity included thromboembolic events (12.5%). Bevacizumab+irinotecan at progression had no responses in 19 patients. While promising, the single-arm design requires confirmation in randomized trials.

Bottom line

Single-agent bevacizumab shows activity in recurrent glioblastoma with 29% PFS6, but bevacizumab+irinotecan at progression had no objective responses.

Strength of evidence

moderate

Recommendation

consider change

Why it matters

  • Phase II single-arm design limits certainty.
  • Historical comparison suggests improvement over prior benchmarks (PFS6 9% vs 29%).
  • Bevacizumab+irinotecan at progression ineffective in this small cohort.

What would change my mind

  • Randomized phase III trial confirming PFS benefit over placebo or standard care.
  • Larger multicenter data with broader patient population.
  • Long-term survival data beyond median follow-up.

Critical appraisal

How strong is the paper?

Methods critique

Risk of bias

High: single-arm design with historical controls introduces selection and performance bias.

Confounding

Moderate: no randomization; prior treatments varied but all were heavily pretreated.

Missing data

Low: all 48 patients assessable for toxicity and response.

Multiplicity

Moderate: multiple secondary endpoints and exploratory analyses without adjustment.

Notes

  • Historical controls used from Wong et al (older) and later consortia studies (PFS6 9%).
  • Companion trial for bevacizumab+irinotecan at progression had separate statistical design.

Stats check

NNT

Not applicable: single-arm trial without direct comparator.

Effect sizes

  • PFS6 29% (95% CI 18% to 48%)
  • Median PFS 16 weeks (95% CI 12 to 26 weeks)
  • Median overall survival 31 weeks (95% CI 21 to 54 weeks)

Absolute effects

  • 48 patients accrued
  • 34 patients (71%) radiographic response by Levin criteria
  • 17 patients (35%) radiographic response by Macdonald criteria
  • 6 patients (12.5%) removed for drug-associated toxicity

Concerns

  • Wide confidence intervals for PFS6 and survival estimates.
  • No statistical comparison to concurrent randomized control group.

External validity

Who it applies to

Heavily pretreated recurrent glioblastoma patients with KPS ≥60%.

Who it does not

Newly diagnosed glioblastoma, patients with acute intracranial hemorrhage or on anticoagulation.

Generalizability notes

  • Single-institution study at NIH Clinical Center.
  • All patients received prior radiotherapy and temozolomide.

Evidence trace

Source trace and metadata

Citations (3)

claim_id

methods_critique.risk_of_bias

locator

p. 2 Patients and Methods

quote

Single-arm phase II trial using historical controls for comparison.

claim_id

stats_check.effect_sizes

locator

p. 3 Results

quote

Median progression-free survival (PFS) was 16 weeks (95% CI, 12 to 26 weeks). The 6-month PFS was 29% (95% CI, 18% to 48%).

claim_id

practice_impact.bottom_line

locator

p. 3 Results

quote

Of 19 patients treated with bevacizumab plus irinotecan at progression, there were no objective radiographic responses.

Metadata

Generated at

2026-03-06T13:41:29.251Z

Version

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