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.
Author(s): Guarneri V(1), Generali DG, Frassoldati A, Artioli F, Boni C, Cavanna L,
Tagliafico E, Maiorana A, Bottini A, Cagossi K, Bisagni G, Piacentini F, Ficarra
G, Bettelli S, Roncaglia E, Nuzzo S, Swaby R, Ellis C, Holford C, Conte P.
Affiliation(s): Author information:
(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.
Publication date & source: 2014, J Clin Oncol. , 32(10):1050-7
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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