Kidney Cancer: Avastin Efficacy Data

Metastatic renal cell carcinoma (mRCC)
Avastin, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma.

AVOREN study results: Avastin plus interferon alfa (IFN) improved median progression-free survival (PFS) by 4.8 months and more than doubled objective response rate (ORR) vs placebo plus IFN[1]

AVOREN study: PFS results[1,13]

  • 4.8-month increase in median PFS: 10.2 months with Avastin plus IFN vs 5.4 months with placebo plus IFN
    • Hazard ratio (HR)=0.60 (95% confidence interval [CI], 0.49–0.72); P<0.0001
  • There was no improvement in median overall survival (OS) with Avastin plus IFN (23 months) vs placebo plus IFN (21 months, HR=0.86 [95% CI, 0.72–1.04] based on the final analysis conducted after 444 deaths[1]
  • The PFS benefit of Avastin plus IFN was observed as early as 2 months and was sustained through the duration of the study[1,14]

PFS was investigator-assessed in the AVOREN trial.[1]

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

AVOREN study: Efficacy data overview[1,3,13,14]

Endpoint   Avastin + IFN Placebo + IFN HR (95% CI) P value
  Number of patients 327 322    
Primary PFS (median) 10.2 months 5.4 months 0.60 (0.49–0.72) <0.0001
Initial primary* OS (median) 23 months 21 months 0.86 (0.72–1.04)  
Secondary ORR 30% (n=306) 12% (n=289)   <0.0001

*The initial primary endpoint was OS, with secondary endpoints including PFS and safety. Based on the approval of new active therapies during the conduct of the trial, which could have confounded OS analyses, it was agreed with regulatory agencies that PFS would become the main outcome measure. There was no improvement in OS.[14]

PFS and ORR were investigator-assessed in the AVOREN trial. [1,13]

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

AVOREN study: A large, multicenter, randomized, double-blind, placebo-controlled Phase III trial[1,14]

IV=intravenous; q2w=every 2 weeks; MIU=million international units; sc=subcutaneous.
Patients in AVOREN were stratified by Memorial Sloan-Kettering Cancer Center score and by country.[14]

  • The initial primary endpoint was OS, with secondary endpoints including PFS and safety[14]
  • Based on the approval of new active therapies during the conduct of the trial, which could have confounded OS analyses, it was agreed with regulatory agencies that PFS would become the main outcome measure[14]
     

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage


In AVOREN, per protocol[1,14]

  • Avastin was continued until disease progression or unacceptable toxicity even if IFN was reduced or discontinued to manage IFN toxicities
  • IFN was discontinued after a maximum of 52 weeks, but Avastin was continued until disease progression or unacceptable toxicity