Valentina Guarneri1, Daniele Giulio Generali, Antonio Frassoldati, Fabrizio Artioli, Corrado Boni, Luigi Cavanna, Enrico Tagliafico, Antonino Maiorana, Alberto Bottini, Katia Cagossi, Giancarlo Bisagni, Federico Piacentini, Guido Ficarra, Stefania Bettelli, Enrica Roncaglia, Simona Nuzzo, Ramona Swaby, Catherine Ellis, Clare Holford, Pierfranco Conte. 1. Valentina Guarneri and PierFranco Conte, Istituto Oncologico Veneto Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), University of Padova, Padova; Daniele Giulio Generali and Alberto Bottini, U.O. Multidisciplinare di Patologia Mammaria, Azienda Ospedaliera Istituti Ospitalieri di Cremona, Cremona; Antonio Frassoldati, University Hospital, Ferrara; Fabrizio Artioli and Katia Cagossi, Ramazzini Hospital, Carpi; Corrado Boni and Giancarlo Bisagni, Azienda Ospedaliera Arcispedale S. Maria Nuova, IRCCS, Reggio Emilia; Luigi Cavanna, Hospital of Piacenza, Piacenza; Enrico Tagliafico, Enrica Roncaglia, and Simona Nuzzo, Center for Genome Research, University of Modena and Reggio Emilia; Antonino Maiorana, Federico Piacentini, Guido Ficarra, and Stefania Bettelli, Modena University Hospital, Modena, Italy; Ramona Swaby and Catherine Ellis, GlaxoSmithKline, Upper Providence, PA; and Clare Holford, GlaxoSmithKline, Stockley Park, United Kingdom.
Abstract
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) -negativeoperable 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, letrozole-lapatinib 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.
RCT Entities:
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, letrozole-lapatinib 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.
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