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document
Gefitinib or placebo in combination with tamoxifen in patients with hormone receptor-positive metastatic breast cancer : a randomized phase II study . PURPOSE Increased growth factor signaling may contribute to tamoxifen resistance . This randomized phase II trial assessed tamoxifen plus placebo or the epidermal growth factor receptor inhibitor gefitinib in estrogen receptor ( ER ) -positive metastatic breast cancer . EXPERIMENTAL DESIGN Patients with newly metastatic disease or recurred after adjuvant tamoxifen ( stratum 1 ) , or recurred during/after adjuvant aromatase inhibitor ( AI ) or after failed first-line AI ( stratum 2 ) , were eligible . Primary variables were progression-free survival ( PFS ; stratum 1 ) and clinical benefit rate ( CBR ; stratum 2 ) . A 5 % or more improvement in response variables with gefitinib was considered to warrant further investigation . Outcome was correlated with biomarkers measured on the primary tumor . RESULTS In stratum 1 ( n = 206 ) , the PFS HR ( gefitinib : placebo ) was 0.84 ( 95 % CI , 0.59-1.18 ; median PFS 10.9 versus 8.8 months ) . In the stratum 1 endocrine therapy-naïve subset ( n = 158 ) the HR was 0.78 ( 95 % CI , 0.52-1.15 ) , and the prior endocrine-treated subgroup ( n = 48 ) 1.47 ( 95 % CI , 0.63-3.45 ) . In stratum 1 , CBRs were 50.5 % with gefitinib and 45.5 % with placebo . In stratum 2 ( n = 84 ) , CBRs were 29.2 % with gefitinib and 31.4 % with placebo . Biomarker analysis suggested that in stratum 1 there was greater benefit with gefitinib in patients who were ER-negative or had lower levels of ER protein . CONCLUSIONS In stratum 1 , the improved PFS with gefitinib plus tamoxifen met the protocol criteria to warrant further investigation of this strategy . In stratum 2 , 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 .
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Intervention_Pharmacological
Gefitinib
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Intervention_Control
placebo
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Intervention_Pharmacological
tamoxifen
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Intervention_Control
placebo
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Intervention_Pharmacological
tamoxifen
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Intervention_Pharmacological
gefitinib
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Intervention_Pharmacological
gefitinib : placebo
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Outcome_Physical
hormone receptor-positive metastatic breast cancer
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Outcome_Mortality
progression-free survival
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Outcome_Physical
clinical benefit rate
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Outcome_Mortality
PFS HR
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Outcome_Mortality
median PFS
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Participant_Condition
metastatic breast cancer
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Participant_Condition
metastatic disease