TY - JOUR
T1 - A phase II randomized study of neoadjuvant letrozole plus alpelisib for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer (NeO-ORB)
AU - Mayer, Ingrid A.
AU - Prat, Aleix
AU - Egle, Daniel
AU - Blau, Sibel
AU - Alejandro Perez Fidalgo, J.
AU - Gnant, Michael
AU - Fasching, Peter A.
AU - Colleoni, Marco
AU - Wolff, Antonio C.
AU - Winer, Eric P.
AU - Singer, Christian F.
AU - Hurvitz, Sara
AU - Estevez, Laura García
AU - Van Dam, Peter A.
AU - Kummel, Sherko
AU - Mundhenke, Christoph
AU - Holmes, Frankie
AU - Babbar, Naveen
AU - Charbonnier, Laure
AU - Diaz-Padilla, Ivan
AU - Vogl, Florian D.
AU - Sellami, Dalila
AU - Arteaga, Carlos L.
N1 - Publisher Copyright:
© 2019 American Association for Cancer Research.
PY - 2019
Y1 - 2019
N2 - Purpose: Addition of alpelisib to fulvestrant significantly extended progression-free survival in PIK3CA-mutant, hormone receptor–positive (HRþ) advanced/metastatic breast cancer in the phase III SOLAR-1 study. The combination of alpelisib and letrozole also had promising activity in phase I studies of HRþ advanced/metastatic breast cancer. NEO-ORB aimed to determine whether addition of alpelisib to letrozole could increase response rates in the neoadjuvant setting. Patients and Methods: Postmenopausal women with HRþ, human epidermal growth factor receptor 2-negative, T1c-T3 breast cancer were assigned to the PIK3CA-wild-type or PIK3CA-mutant cohort according to their tumor PIK3CA status, and randomized (1:1) to 2.5 mg/day letrozole with 300 mg/day alpelisib or placebo for 24 weeks. Primary endpoints were objective response rate (ORR) and pathologic complete response (pCR) rate for both PIK3CA cohorts. Results: In total, 257 patients were assigned to letrozole plus alpelisib (131 patients) or placebo (126 patients). Grade 3 adverse events (5% of patients) in the alpelisib arm were hyperglycemia (27%), rash (12%), and maculopapular rash (8%). The primary objective was not met; ORR in the alpelisib versus placebo arm was 43% versus 45% and 63% versus 61% in the PIK3CA-mutant and wild-type cohorts, respectively. pCR rates were low in all groups. Decreases in Ki-67 were similar across treatment arms and cohorts. In PIK3CA-mutant tumors, alpelisib plus letrozole treatment induced a greater decrease in phosphorylated AKT versus placebo plus letrozole. Conclusions: In contrast to initial results in advanced/metastatic disease, addition of alpelisib to 24-week neoadjuvant letrozole treatment did not improve response in patients with HRþ early breast cancer.
AB - Purpose: Addition of alpelisib to fulvestrant significantly extended progression-free survival in PIK3CA-mutant, hormone receptor–positive (HRþ) advanced/metastatic breast cancer in the phase III SOLAR-1 study. The combination of alpelisib and letrozole also had promising activity in phase I studies of HRþ advanced/metastatic breast cancer. NEO-ORB aimed to determine whether addition of alpelisib to letrozole could increase response rates in the neoadjuvant setting. Patients and Methods: Postmenopausal women with HRþ, human epidermal growth factor receptor 2-negative, T1c-T3 breast cancer were assigned to the PIK3CA-wild-type or PIK3CA-mutant cohort according to their tumor PIK3CA status, and randomized (1:1) to 2.5 mg/day letrozole with 300 mg/day alpelisib or placebo for 24 weeks. Primary endpoints were objective response rate (ORR) and pathologic complete response (pCR) rate for both PIK3CA cohorts. Results: In total, 257 patients were assigned to letrozole plus alpelisib (131 patients) or placebo (126 patients). Grade 3 adverse events (5% of patients) in the alpelisib arm were hyperglycemia (27%), rash (12%), and maculopapular rash (8%). The primary objective was not met; ORR in the alpelisib versus placebo arm was 43% versus 45% and 63% versus 61% in the PIK3CA-mutant and wild-type cohorts, respectively. pCR rates were low in all groups. Decreases in Ki-67 were similar across treatment arms and cohorts. In PIK3CA-mutant tumors, alpelisib plus letrozole treatment induced a greater decrease in phosphorylated AKT versus placebo plus letrozole. Conclusions: In contrast to initial results in advanced/metastatic disease, addition of alpelisib to 24-week neoadjuvant letrozole treatment did not improve response in patients with HRþ early breast cancer.
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U2 - 10.1158/1078-0432.CCR-18-3160
DO - 10.1158/1078-0432.CCR-18-3160
M3 - Article
C2 - 30723140
AN - SCOPUS:85064941338
SN - 1078-0432
VL - 25
SP - 2975
EP - 2987
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -