ASCO: Small Survival Benefit for Bevacizumab (Avastin) Plus Chemotherapy in NSCLC

CHICAGO, June 2 -- Adding bevacizumab (Avastin) to chemotherapy improved progression-free-survival for non-small-cell lung cancer by 33%, an absolute increase of about 21 days, found a European trial.

To get the 33% improvement (P=0.0026), bevacizumab was given at 7.5 mg/kg, said Christian Manegold, M.D., of the University of Heidelberg in Germany, who revealed results of the AVAiL (Avastin in Lung cancer) trial at a late-breaking trials session at the American Society of Clinical Oncology meeting here.

Patients given 15 mg/kg of bevacizumab had an improved progression-free survival of 22%, an absolute increase of about two weeks. This, too, was statistically significant (P=0.0301).

Moreover, bevacizumab therapy was associated with a more durable tumor response-6.1 months versus 4.7 months, he said.

Dr. Manegold said that the results replicate findings of a study by the Eastern Cooperative Oncology Group (ECOG) that bevacizumab was an effective adjunct to the standard chemotherapy.

But Dr. Manegold noted that because "the confidence intervals in both bevacizumab arms cross, we can say there was an added benefit with bevacizumab, but we cannot recommend a specific dose."

For now, he recommended following FDA-approved indications--15 mg/kg of bevacizumab every three weeks in combination with platinum-based therapy (carboplatin and paclitaxel (Taxol]).

Asked about the small absolute improvement, Dr. Manegold pointed out that benefit in NSCLC always comes in small increments that are measured in days and weeks, not years.

AVAiL randomized 1,044 patients with treatment-nave advanced NSCLC to chemotherapy with cisplatin (Platinol) at 80 mg/m² on day one and gemcitabine (Gemzar) at 1,250 mg/m² on day one and day eight every three weeks, for up to six cycles. In addition patients received bevacizumab at one of the two study doses or placebo.

The primary endpoint was progression-free survival, which was defined as the time from randomization to first event of progression or death. Secondary endpoints included overall survival, time to treatment failure, and safety.

Patients were randomized from February 2005 through August 2006. Three hundred and forty five patients received low-dose bevacizumab, 351 received the 15 mg/kg dose, and 347 patients were in the control arm.

Among the findings:

• Censoring for non-protocol anti-neoplastic therapy prior to progression, there was a 30% increase in survival in the 7.5 mg/kg arm (P=0.0004) and a 22% increase in the 15 mg/kg arm (P=0.0125).
• The tumor response rate as 34% in the 7.5 mg/kg arm, 30% in the 15 mg/kg arm, and 20% in the control arm.
• Six percent of patients in the low-dose bevacizumab arm and 9% of patients in high-dose arm had grade 3 or higher hypertensions, versus 2% of control patients.
• There were four treatment-related deaths in the control and low dose bevacizumab arms and five in the 15 mg/kg arm.