Double-blind, placebo-controlled, multicenter, randomized, phase IIB neoadjuvant study of letrozole-lapatinib in postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative, operable breast cancer

Purpose: This is a randomized, double-blind, placebo-controlled study aimed to evaluate the clinical and biologic effects of letrozole plus lapatinib or placebo as neoadjuvant therapy in hormone receptor (HR) -positive/human epidermal growth factor receptor 2 (HER2) -negative operable breast cancer. Methods: Ninety-two postmenopausal women with stage II to IIIA primary breast cancer were randomly assigned to preoperative therapy consisting of 6 months of letrozole 2.5 mg orally daily plus lapatinib 1,500 mg orally daily or placebo. Surgery was performed within 2 weeks from the last study medication. Clinical response was assessed by ultrasonography. Pre- and post-treatment samples were evaluated for selected biomarkers. Fresh-frozen tissue samples were collected for genomic analyses. Results: Numerically similar clinical response rates (partial + complete response) were observed (70% for letrozole-lapatinib and 63% for letrozole-placebo). Toxicities were generally mild and manageable. A significant decrease in Ki-67 and pAKT expression from baseline to surgery was observed in both arms. Overall, 34 patients (37%) had a mutation in PIK3CA exon 9 or 20. In the letrozole-lapatinib arm, the probability of achieving a clinical response was significantly higher in the presence of PIK3CA mutation (objective response rate, 93% v 63% in PIK3CA wild type; P = .040). Conclusion: The combination of letrozole-lapatinib in early breast cancer was feasible, with expected and manageable toxicities. In unselected estrogen receptor-positive/ HER2-negative patients, letrozolelapatinib and letrozole-placebo resulted in a similar overall clinical response rate and similar effect on Ki-67 and pAKT. Our secondary end point findings of a significant correlation between PIK3CA mutation and response to letrozole-lapatinib in HR-positive/HER2-negative early breast cancer must now be independently confirmed. © 2014 by American Society of Clinical Oncology.

Data di pubblicazione: 2014
Titolo: Double-blind, placebo-controlled, multicenter, randomized, phase IIB neoadjuvant study of letrozole-lapatinib in postmenopausal hormone receptor-positive, human epidermal growth factor receptor 2-negative, operable breast cancer
Autori: Guarneri, Valentina; Generali, Daniele Giulio; Frassoldati, Antonio; Artioli, Fabrizio; Boni, Corrado; Cavanna, Luigi; Tagliafico, Enrico; Maiorana, Antonino; Bottini, Alberto; Cagossi, Katia; Bisagni, Giancarlo; Piacentini, Federico; Ficarra, Guido; Bettelli, Stefania; Roncaglia, Enrica; Nuzzo, Simona; Swaby, Ramona; Ellis, Catherine; Holford, Clare; Conte, Pierfranco
Rivista: JOURNAL OF CLINICAL ONCOLOGY
Parole Chiave: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Breast Neoplasms; Double-Blind Method; Female; Humans; Ki-67 Antigen; Middle Aged; Mutation; Neoadjuvant Therapy; Nitriles; Phosphatidylinositol 3-Kinases; Phosphorylation; Postmenopause; Proto-Oncogene Proteins c-akt; Quinazolines; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Triazoles; Cancer Research; Oncology; Medicine (all)
Abstract in inglese: Purpose: This is a randomized, double-blind, placebo-controlled study aimed to evaluate the clinical and biologic effects of letrozole plus lapatinib or placebo as neoadjuvant therapy in hormone receptor (HR) -positive/human epidermal growth factor receptor 2 (HER2) -negative operable breast cancer. Methods: Ninety-two postmenopausal women with stage II to IIIA primary breast cancer were randomly assigned to preoperative therapy consisting of 6 months of letrozole 2.5 mg orally daily plus lapatinib 1,500 mg orally daily or placebo. Surgery was performed within 2 weeks from the last study medication. Clinical response was assessed by ultrasonography. Pre- and post-treatment samples were evaluated for selected biomarkers. Fresh-frozen tissue samples were collected for genomic analyses. Results: Numerically similar clinical response rates (partial + complete response) were observed (70% for letrozole-lapatinib and 63% for letrozole-placebo). Toxicities were generally mild and manageable. A significant decrease in Ki-67 and pAKT expression from baseline to surgery was observed in both arms. Overall, 34 patients (37%) had a mutation in PIK3CA exon 9 or 20. In the letrozole-lapatinib arm, the probability of achieving a clinical response was significantly higher in the presence of PIK3CA mutation (objective response rate, 93% v 63% in PIK3CA wild type; P = .040). Conclusion: The combination of letrozole-lapatinib in early breast cancer was feasible, with expected and manageable toxicities. In unselected estrogen receptor-positive/ HER2-negative patients, letrozolelapatinib and letrozole-placebo resulted in a similar overall clinical response rate and similar effect on Ki-67 and pAKT. Our secondary end point findings of a significant correlation between PIK3CA mutation and response to letrozole-lapatinib in HR-positive/HER2-negative early breast cancer must now be independently confirmed. © 2014 by American Society of Clinical Oncology.
Digital Object Identifier (DOI): 10.1200/JCO.2013.51.4737
Handle: http://hdl.handle.net/11392/2377792
Appare nelle tipologie:03.1 Articolo su rivista

File in questo prodotto:
Non ci sono file associati a questo prodotto.
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
 
 
 
Powered by IRIS-about IRIS-Utilizzo dei cookie
Logo CINECA  Copyright © 2022