Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer: A randomized phase II study Full Text
Clinical Cancer Research, 01/12/2011
Clinical Article
Osborne CK et al. – In St1, the improved PFS with gefitinib plus tamoxifen met the protocol criteria sufficient to warrant further investigation of this strategy. In St2, there was a numerical disadvantage for gefitinib; additional investigation after AI therapy is not warranted. Studies of predictive biomarkers are needed to subset appropriate patients.
Methods- Patients with newly metastatic disease or recurring after adjuvant tamoxifen (Stratum 1, St1), or recurred during/after adjuvant aromatase inhibitor (AI) or after failed first-line AI (Stratum 2,St2) were eligible
- Primary variables PFS (St1) and clinical benefit rate (CBR) (St2)
- ≥ 5% improvement in response variables with gefitinib considered to warrant further investigation
- Outcome correlated with biomarkers measured on primary tumor
- In St1 (n=206), the PFS hazard ratios (HR, gefitinib:placebo) were 0.84 (95% CI, 0.59 to 1.18; median PFS 10.9 v 8.8 months)
- In the St1 endocrine therapy naïve subset (n=158) the HR 0.78 (95% CI, 0.52 to 1.15), and prior endocrine-treated subgroup (n=48) 1.47 (95% CI, 0.63 to 3.45)
- In St1, CBRs were 50.5% with gefitinib and 45.5% with placebo
- In St2 (n=84), CBRs were 29.2% with gefitinib and 31.4% with placebo
- Biomarker analysis suggested that in St1 greater benefit with gefitinib in patients ER negative or had lower levels of ER protein
