A Randomized Phase II Trial Comparing RhuMAb VEGF (Recombinant Humanized Monoclonal Antibody to Vascular Endothelial Cell Growth Factor) Plus Carboplatinum/Paclitaxel (CP) to CP Alone in Patients with Stage IIIB/IV Non-small Cell Lung Cancer
Bradley Somer, MD
OncoLink Assistant Editor
Last Modified: May 23, 2000
Presenter: Russel DeVore, MD
Affiliation: Vanderbilt University
For advanced and metastatic non-small cell lung cancer, current therapies are limited. These therapies at best may offer patients survival benefits on the order of approximately 4 months, and can still have side effects which may be serious. Newer therapies are in trials which attempt to enhance survival and limit toxicities. This report was of a phase II study looking at a novel angiogenesis inhibitor utilizing monoclonal antibody against vascular endothelial growth factor (VEGF). The drug works by neutralizing VEGF, consequently stopping new blood vessel formation which thus limits the blood supply to the tumor.
Materials and Methods:
- 99 patients had advanced NSCLC ?Stage IIIB/IV and were chemotherapy naïve.
- Patients were randomized to 1 of 3 groups: - Control: Carboplatinum (AUC6)/paclitaxel (200mg/m2) [CP] alone every 3 wks x 6 cycles- 32 patients. - CP plus low dose rhuMAb VEGF ? 7.5mg/kg every 3 weeks ? 32 patients. - CP plus high dose rhuMAb VEGF ? 15 mg/kg every 3 weeks ? 35 patients.
- Results were reported by investigators and additionally by blinded reviewers
- Time to progression was 4.2 month in the control treatment arm, 4.3 months in the low dose arm and 7.4 months in the high dose arm.
- Response rates were 18.8% in the control arm, 28% in the low dose arm and 31.5% in the high dose anti-VEGF arm.
- There were 6 cases of life threatening hemoptysis (lung bleeding) in those patients who were treated with Anti-VEGF, 4 of whom died. 4 of these patients had squamous cell histology in spite of the fact that only 19% of the initial enrollees had this subtype.
- These data support the notion that antiangiogenesis drugs may improve outcomes. - A larger phase III study using only the high dose arm is needed.
- Further studies may require elimination of patients with squamous cell carcinoma because of hemoptysis or may require pretreatment with other forms of therapy e.g. radiation therapy.
- New molecular targeting agents suggest a potential next wave of improvement over traditional cytotoxic therapies.
- New studies are being done with this agent in breast and colon cancer.