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.

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 / 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 Raffaella; Roncaglia, Enrica; Nuzzo, Simona; Swaby, Ramona; Ellis, Catherine; Holford, Clare; Conte, Pierfranco. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - ELETTRONICO. - 32:(2014), pp. 1050-7-1057. [10.1200/JCO.2013.51.4737]

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

TAGLIAFICO, Enrico;MAIORANA, Antonino;PIACENTINI, Federico;BETTELLI, Stefania Raffaella;RONCAGLIA, Enrica;NUZZO, Simona;
2014

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) –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.
32
1050-7
1057
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 / 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 Raffaella; Roncaglia, Enrica; Nuzzo, Simona; Swaby, Ramona; Ellis, Catherine; Holford, Clare; Conte, Pierfranco. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - ELETTRONICO. - 32:(2014), pp. 1050-7-1057. [10.1200/JCO.2013.51.4737]
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 Raffaella; Roncaglia, Enrica; Nuzzo, Simona; Swaby, Ramona; Ellis, Catherine; Holford, Clare; Conte, Pierfranco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1060827
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