Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy.

Pistilli, B.; Pluard, T.; Urruticoechea, A.; Farci, D.; Kong, A.; Bachelot, T.; Chan, S.; Han, H. S.; Jerusalem, Guy; Urban, P.; Robinson, D.; Mouhaer, S. L.; Tomaso, E. D.; Massacesi, C.; Saura, C.

doi:10.1007/s10549-017-4596-7

Article (Scientific journals)

Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy.

Pistilli, B.; Pluard, T.; Urruticoechea, A. et al.

2017 • In Breast Cancer Research and Treatment

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/218352

DOI
10.1007/s10549-017-4596-7

PubMed
29198055

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Keywords :

Advanced/metastatic breast cancer; Brain metastases; Buparlisib; HER2-positive; Herceptin; Trastuzumab pretreated

Abstract :

[en] PURPOSE: A Phase Ib study in patients with trastuzumab-resistant, human epidermal growth factor receptor-2- (HER2)-positive advanced breast cancer defined the recommended Phase II dose of buparlisib as 100 mg/day in combination with 2 mg/kg weekly trastuzumab, and reported preliminary signs of clinical activity. Here we present results from the Phase II portion. METHODS: Patients with trastuzumab-resistant, HER2-positive advanced breast cancer received buparlisib plus trastuzumab. Study endpoints included safety/tolerability and antitumour activity. The study was extended to include a Phase Ib dose-escalation phase, in which patients with progressive brain metastases also received capecitabine. RESULTS: In the Phase II portion, of 50 patients treated with buparlisib and trastuzumab, the most common (>/= 30%) all-grade adverse events (AEs) were diarrhoea (54%), nausea (48%), decreased appetite, increased alanine aminotransferase (36% each), increased aspartate aminotransferase (34%), fatigue, rash (32% each), cough and hyperglycemia (30% each). One (2%) patient achieved complete response and four (8%) patients had confirmed partial responses [PR; including two patients with phosphatidylinositol 3-kinase (PI3 K) pathway-activated tumours]. Overall response rate (ORR) was 10%: the primary endpoint (ORR >/= 25%) was therefore not met. In the Phase Ib portion, all patients with measurable brain lesions at baseline showed tumour shrinkage to some degree; due to low enrollment, maximum tolerated dose of buparlisib in combination with trastuzumab and capecitabine was not determined. CONCLUSION: Buparlisib plus trastuzumab, as a chemotherapy-free regimen, demonstrated an acceptable safety profile but limited efficacy in patients with heavily pretreated, trastuzumab-resistant HER2-positive breast cancer, and in patients with progressive brain metastases also receiving capecitabine.

Disciplines :

Oncology

Author, co-author :

Pistilli, B.

Pluard, T.

Urruticoechea, A.

Farci, D.

Kong, A.

Bachelot, T.

Chan, S.

Han, H. S.

Jerusalem, Guy ; Université de Liège - ULiège > Département des sciences cliniques > Oncologie

Urban, P.

More authors (5 more)

Language :

English

Title :

Phase II study of buparlisib (BKM120) and trastuzumab in patients with HER2+ locally advanced or metastatic breast cancer resistant to trastuzumab-based therapy.

Publication date :

2017

Journal title :

Breast Cancer Research and Treatment

ISSN :

0167-6806

eISSN :

1573-7217

Publisher :

Kluwer Academic Publishers, Netherlands

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 16 January 2018

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