Pazopanib Fails to Prolong Progression-Free Survival in Recurrent Glioblastoma Study

Strategic Insights -

Researchers conducted a phase II trial to evaluate the efficacy and safety of pazopanib, a multi-targeted angiogenesis inhibitor, in adults with recurrent glioblastoma. The study, led by F.M. Iwamoto and colleagues at the National Cancer Institute, aimed to assess the progression-free survival (PFS) of patients treated with pazopanib. The trial involved 35 patients with a median age of 53 years and a median Karnofsky performance scale of 90.

Key Takeaways:

  • The primary endpoint of the study was efficacy as measured by 6-month progression-free survival (PFS6), which was not achieved in the patients treated with pazopanib.
  • Grade 3/4 toxicities included leukopenia (n=1), lymphopenia (n=2), thrombocytopenia (n=1), ALT elevation (n=3), AST elevation (n=1), CNS hemorrhage (n=1), fatigue (n=1), and thrombotic/embolic events (n=3); 8 patients required dose reduction.
  • Two patients had a partial radiographic response by standard bidimensional measurements, while 9 patients showed decreased contrast enhancement, vasogenic edema, and mass effect but failed to achieve 6 months of PFS.
  • Thirty patients (86%) had died, and the median survival was 35 weeks (95% CI: 24-47 weeks).
  • Pazopanib showed in situ biological activity as demonstrated by radiographic responses, but it was not sufficient to prolong PFS in this patient population.
  • The study demonstrated that pazopanib was reasonably well tolerated with a spectrum of toxicities similar to other anti-VEGF/VEGFR agents.

Statistics:

  • 35 patients were accrued in the study with a median age of 53 years and a median Karnofsky performance scale of 90.
  • 8 patients required dose reduction due to toxicities.
  • 2 patients had a partial radiographic response.
  • 9 patients showed decreased contrast enhancement, vasogenic edema, and mass effect.
  • 30 patients (86%) had died, and the median survival was 35 weeks (95% CI: 24-47 weeks).
  • Pazopanib did not prolong PFS6 in the study population.

Sources:

  • "Phase II trial of pazopanib (GW786034), an oral multi-targeted angiogenesis inhibitor, for adults with recurrent glioblastoma (North American Brain Tumor Consortium Study 06-02)," Neuro-oncology, 2010;12(8):855-61.
  • ClinicalTrials.gov identifier: NCT00459381.