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Journal Club

Tumor/Skull Base

Phase III Randomized Trial Comparing the Efficacy of Cediranib As Monotherapy, and in Combination With Lomustine, Versus Lomustine Alone in Patients With Recurrent Glioblastoma

J Clin Oncol | 2013

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.2012.47.2464

PMID

23940216

PICO

Population

Patients with recurrent glioblastoma who previously received radiation and temozolomide

Intervention

Cediranib monotherapy (30 mg) or cediranib (20 mg) plus lomustine (110 mg/m²)

Comparator

Lomustine (110 mg/m²) plus placebo

Outcomes

Progression-free survival (primary), overall survival, time to deterioration in neurologic status, corticosteroid-sparing effects

Design

Type

Randomized controlled trial

Randomized

Yes

Multicenter

Yes

Blinded

Partially blinded (placebo-controlled for lomustine arm; independent radiographic assessment blinded)

Follow-up

Not specified in excerpt; follow-up until progression or death

Primary endpoint

Progression-free survival based on blinded, independent radiographic assessment of postcontrast T1-weighted and noncontrast T2-weighted MRI brain scans

Secondary endpoints

  • Overall survival
  • Time to deterioration in neurologic status
  • Corticosteroid-sparing effects

Practice impact

What this means

This phase III trial (REGAL) randomized 325 patients with recurrent GBM to cediranib (VEGF inhibitor) monotherapy, cediranib plus lomustine, or lomustine alone. Neither cediranib arm significantly improved progression-free survival versus lomustine alone. While cediranib showed some steroid-sparing effects, it should not replace current standard therapies for recurrent GBM.

Bottom line

Cediranib, alone or with lomustine, did not significantly improve PFS versus lomustine alone in recurrent GBM.

Strength of evidence

high

Recommendation

do not change

Why it matters

  • Phase III RCT with negative primary endpoint
  • No survival benefit demonstrated
  • Some secondary benefits (steroid reduction) do not outweigh lack of efficacy on primary outcome

What would change my mind

  • Subgroup analysis showing significant PFS benefit in molecularly defined populations
  • Subsequent meta-analysis demonstrating overall survival benefit
  • New trial with different dosing or combination regimen showing efficacy

Critical appraisal

How strong is the paper?

Methods critique

Risk of bias

Low risk for selection and performance bias due to randomization and partial blinding; detection bias minimized by independent blinded radiographic review

Confounding

Randomization likely balanced known confounders; no major imbalances reported

Missing data

Not explicitly addressed in excerpt; intention-to-treat analysis implied

Multiplicity

Two primary comparisons (cediranib monotherapy vs lomustine; combination vs lomustine) without adjustment for multiple testing noted

Notes

  • Industry-funded (AstraZeneca) with authors employed by sponsor
  • Partially blinded design may introduce bias in patient-reported outcomes

Stats check

NNT

N/A

Effect sizes

  • HR 1.05 (95% CI 0.74-1.50) for cediranib monotherapy vs lomustine
  • HR 0.76 (95% CI 0.53-1.08) for cediranib plus lomustine vs lomustine

Absolute effects

  • Sample size N=325
  • PFS not significantly different for either comparison (two-sided P=0.90 and P=0.16)

Concerns

  • Primary endpoint not met; confidence intervals cross 1.0 for both comparisons
  • No adjustment for multiple comparisons on primary endpoint

External validity

Who it applies to

Adult patients with recurrent glioblastoma after standard chemoradiation, similar to trial population

Who it does not

Patients with newly diagnosed GBM, non-recurrent disease, or significant comorbidities

Generalizability notes

  • Multicenter international study enhances generalizability
  • Excludes patients with prior anti-VEGF therapy

Evidence trace

Source trace and metadata

Citations (3)

claim_id

methods_critique.risk_of_bias

locator

p. 1 Methods

quote

blinded, independent radiographic assessment

claim_id

stats_check.effect_sizes

locator

p. 1 Results

quote

HR = 1.05; 95% CI, 0.74 to 1.50; two-sided P = .90

claim_id

practice_impact.bottom_line

locator

p. 1 Results

quote

This study did not meet its primary end point of PFS prolongation with cediranib

Metadata

Generated at

2026-03-06T13:41:29.251Z

Version

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