MEN1611, a PI3K inhibitor, combined with trastuzumab (T) +/- fulvestrant (F) for HER2+/PIK3CA mutant (mut) advanced or metastatic (a/m) breast cancer (BC): Safety and efficacy results from the ongoing phase Ib study (B-PRECISE-01)
Authors
Piccart, M.Borrego, M. R.
Arkenau, H. T.
Escriva-De-Romani, S. I.
Howell, Sacha J
Hennequin, A.
Jimenez-Rodriguez, B.
Del Conte, G.
Simonelli, M.
Palleschi, M.
Duhoux, F.
Uribe, B.
Curigliano, G.
Waters, S.
Aftimos, P. G.
Wildiers, H.
Tosi, D.
Amair-Pinedo, F.
Pellacani, A. U. E.
Laurent, D. O.
Affiliation
Medical Oncology Clinic, Institute Jules Bordet, Brussels, BelgiumIssue Date
2021
Metadata
Show full item recordAbstract
Background MEN1611 (MEN) is an oral PI3K inhibitor active on the p110? mut and WT, ? and ? isoforms, while sparing the ?. B-PRECISE-01 is an ongoing phase 1b study investigating MEN in combination with T � F. No dose-limiting toxicities (DLTs) were observed during the escalation step and MEN 48 mg BID was selected as Recommended Phase 2 Dose (R2PD) for cohort expansion (CE). Methods In this open-label, 2-arm study, eligible patients (pts) had HER2+/PIK3CAmut locally unresectable advanced or metastatic (a/m) BC and were treated with at least 2 prior anti-HER2 therapies in the metastatic setting including T. All pts received MEN+T, while F was added in hormone receptor positive (HR+) postmenopausal women. Pooled safety and efficacy data from the two subpopulations of CE are presented herein. Results As of March 2021, 42 female pts were treated: 36 of them with MEN 48 mg BID (18 MEN+T and 18 MEN+T+F). Median age 55 years (range 34-78), 25% premenopausal, ECOG PS 0-1: 95.2%. Median metastatic regimes 4; 57.1% had prior pertuzumab and 73.8% had prior T-DM1. Common treatment-emergent adverse events (TEAEs, ?20%) were diarrhea 64.3%, nausea 42.8%, asthenia 31%, decreased appetite 28.6%, anemia 28.6%, and hyperglycemia 23.8%. Most treatment-related AE (TRAEs) were reversible and manageable by supportive care. TRAEs caused treatment interruption in 14 pts (33.3%, 1 pt definitely) and dose reduction in 6 pts (16.7%, only allowed in CE) mostly hyperglycemia, diarrhea, nausea, asthenia and decreased appetite. Serious TRAEs were experienced by 8 pts (19%): hyperglycemia 3 pts, diarrhea 2 pts, general physical health deterioration, generalized edema, and pneumonitis (1 pt each). In the efficacy-evaluable population (n=29) 9 pts showed partial response (MEN+T 4/11, MEN+T+F 5/18), and 18 pts had stable disease (MEN+T 6/11, MEN+T+F 10/18) as best response. Seven pts were on treatment > 6 months (MEN+T 3, MEN+T+F 4), and 1 pt received MEN+T > 12 months. Conclusions MEN combined with T � F shows a manageable safety profile with encouraging duration of antitumoral activity in heavily pre-treated pts with HER2+/PIK3CAmut a/m BC. Recruitment for CE is open.Citation
Piccart M, Ruiz Borrego M, Arkenau H-T, Escriv�-de-Roman� SI, Howell SJ, Hennequin A, et al. 266P MEN1611, a PI3K inhibitor, combined with trastuzumab (T) � fulvestrant (F) for HER2+/PIK3CA mutant (mut) advanced or metastatic (a/m) breast cancer (BC): Safety and efficacy results from the ongoing phase Ib study (B-PRECISE-01). Vol. 32, Annals of Oncology. Elsevier BV; 2021. p. S478�9.Journal
Annals of OncologyDOI
10.1016/j.annonc.2021.08.549Additional Links
https://dx.doi.org/10.1016/j.annonc.2021.08.549Type
OtherLanguage
enae974a485f413a2113503eed53cd6c53
10.1016/j.annonc.2021.08.549