Phase II, Randomized Trial to Compare Anastrozole Combined with Gefitinib or Placebo in Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer

• Published in: Clinical cancer research Vol. 16; no. 6; pp. 1904 - 1914
• Main Authors: CRISTOFANILLI, Massimo, VALERO, Vicente, CORA, Elsa M, ANDERSON, Elizabeth, MAGILL, Patrick J, MANGALIK, Aroop, ROYCE, Melanie, RABINOWITZ, Ian, ARENA, Francis P, KROENER, Joan F, CURCIO, Elizabeth, WATKINS, Claire, BACUS, Sarah
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15-03-2010
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - pharmacokinetics; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Double-Blind Method; Female; Gynecology. Andrology. Obstetrics; Humans; Lymphatic Metastasis; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent - drug therapy; Neoplasms, Hormone-Dependent - metabolism; Neoplasms, Hormone-Dependent - pathology; Nitriles - administration & dosage; Pharmacology. Drug treatments; Postmenopause; Prospective Studies; Quinazolines - administration & dosage; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2 - metabolism; Receptors, Estrogen - metabolism; Receptors, Progesterone - metabolism; Survival Rate; Tissue Distribution; Treatment Outcome; Triazoles - administration & dosage; Tumors; Antineoplastic agent; Breast disease; Azole derivatives; Quinazoline derivatives; Menopause; Antiestrogen; Antihormone; Estrogen synthase; Metastasis; Randomization; Phase II trial; Postmenopause; Adult; Female; Advanced stage; Woman; Gefitinib; Non steroid compound; Protein-tyrosine kinase; Human; Drug combination; Aromatase inhibitor; Enzyme; Tyrosine kinase inhibitor; Anastrozole; Transferases; Enzyme inhibitor; Breast cancer; Malignant tumor; Mammary gland diseases; Placebo; Triazole derivatives; Cancer; Hormonal receptor
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-09-2282

This phase II randomized trial evaluated the efficacy and tolerability of anastrozole combined with gefitinib or anastrozole with placebo in women with hormone receptor-positive metastatic breast cancer (MBC).
Postmenopausal women with hormone receptor-positive measurable or evaluable MBC who had not received prior endocrine therapy for this disease stage or who developed metastatic disease during/after adjuvant tamoxifen were eligible. The primary response variable was progression-free survival (PFS) and secondary response variables included clinical benefit rate, objective response rate, overall survival, safety and tolerability, and pharmacokinetics. Tumor biomarker evaluation was an exploratory objective.
Forty-three patients were randomized to anastrozole plus gefitinib and 50 patients were randomized to anastrozole plus placebo of a planned total of 174 patients (enrollment was prematurely discontinued due to slow recruitment). PFS for patients receiving the combination of anastrozole and gefitinib was longer than for patients receiving anastrozole plus placebo [hazard ratio (gefitinib/placebo), 0.55; 95% confidence interval, 0.32-0.94; median PFS, 14.7 versus 8.4 months]. The clinical benefit rate was 49% versus 34%, and the objective response rate was 2% versus 12% with anastrozole plus gefitinib and anastrozole plus placebo, respectively. No evidence of interaction between baseline biomarker levels and relative treatment effect was found. No unexpected adverse events were observed.
This small randomized study showed that anastrozole in combination with gefitinib is associated with a marked advantage in PFS compared with anastrozole plus placebo, and that the combination was tolerated in postmenopausal women with hormone receptor-positive MBC. Further investigation of epidermal growth factor receptor inhibition in combination with endocrine therapy may be warranted.