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ePoster Display Session

129TiP - Metformin (MF) in the prevention of hyperglycemia (HG) in patients (pts) with PIK3CA-mutated, hormone receptor (HR)[+]/HER2[-] advanced breast cancer (ABC) treated with alpelisib (ALP) plus fulvestrant (F): METALLICA

Date

05 May 2021

Session

ePoster Display Session

Presenters

Antonio Llombart

Citation

Annals of Oncology (2021) 32 (suppl_2): S60-S78. 10.1016/annonc/annonc508

Authors

A. Llombart1, J.M. Pérez-Garcia2, S. Blanch3, P. Tolosa4, M. Ruiz Borrego5, M. Gion Cortes6, A. Fernádez7, A. Urruticoechea8, E. Galve9, J.F. Cueva Banuelos10, J. Ponce11, J.L. Alonso12, M. Capelán13, E. Martínez14, B. Bermejo De Las Heras15, B. Rojas16, T. Martos17, A. López18, F. Gómez-Peralta19, J. Cortes Castan20

Author affiliations

  • 1 Valencia/ES
  • 2 International Breast Cancer Center (IBCC), Quiron Group, 8018 - Barcelona/ES
  • 3 Oncology Valencian Institute, 46009 - Valencia/ES
  • 4 University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 5 Hospital Universitario Virgen del Rocio, 41013 - Seville/ES
  • 6 Hospital Universitario Ramon y Cajal, 28031 - Madrid/ES
  • 7 ICO - Institut Català d'Oncologia l'Hospitalet (Hospital Duran i Reynals), 8908 - Hospitalet de Llobregat/ES
  • 8 Onkologikoa, 20014 - Donostia/ES
  • 9 Hospital Universitario Basurto (OSI Bilbao-Basurto), 48013 - Bilbao/ES
  • 10 CHUS - Complejo Hospitalario Universitario de Santiago de Compostela SERGAS, 15706 - Santiago de Compostela/ES
  • 11 Hospital General Universitario de Alicante, 3010 - Hospital General Universitario de Alicante/ES
  • 12 Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Murcia, 30120 - El Palmar/ES
  • 13 Vall d’Hebron Institute of Oncology (VHIO), 8035 - Barcelona/ES
  • 14 Consorcio Hospitalario Provincial de Castellón, 12002 - Castellón de la Plana/ES
  • 15 Hospital Clinico Universitario de Valencia, 46010 - Valencia/ES
  • 16 HM CIOCC, 28050 - Madrid/ES
  • 17 Hospital del Mar, 8003 - Barcelona/ES
  • 18 University Hospital of León, 24071 - León/ES
  • 19 Hospital General de Segovia, 40002 - Segovia/ES
  • 20 Vall d'Hebron University Hospital, 8035 - Barcelona/ES
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Abstract 129TiP

Background

ALP is an α-specific PI3K-α inhibitor, that has shown to significantly increase the median progression-free survival (PFS) when combined with F in pts with PIK3CA-mutated, HR[+]/HER2[–] ABC who had failed to an aromatase inhibitor (AI) regimen. HG is an on-target effect of the PI3K inhibition, being the most frequent adverse event (AE) of grade (G)3/4 and the most common AE leading to discontinuation of ALP in the randomized, phase III SOLAR-1 study. MF is approved for pts with diabetes mellitus (DM) and represented the preferred option for treating ALP-induced HG in the SOLAR-1 study. METALLICA is evaluating the effect of MF in the prevention of HG in PIK3CA-mutated, HR[+]/HER2[–] ABC pts under treatment with ALP plus F.

Trial design

This is a multicenter, open-label, two-cohort, Simon’s two-stage design, phase II trial. Main selection criteria include: (1) Pts ≥ 18 years diagnosed with AI-resistant, PIK3CA-mutated, HR[+]/HER2[–] ABC; (2) No prior history of type I/II DM requiring anti-diabetic drugs; (3) ≤1 prior line of chemotherapy for ABC and/or no prior treatment with any PI3K inhibitor and/or F. A total of 68 pts will be enrolled into two study cohorts according to the baseline glycaemia status: (A) 48 pts with fasting glycaemia <100 mg/dL and glycosylated hemoglobin (HbA1c) < 5.7%; (B) 20 pts with fasting glycaemia 100–140 mg/dL and/or HbA1c 5.7–6.4%. Pts will receive ALP (300mg, orally, once daily) plus F (500mg, intramuscular injection on days 1, 15 of cycle 1 and on day 1 thereafter) and MF (500mg, twice a day (BID) on days 1–3 and 1000mg BID thereafter). The primary endpoint is the rate of G3/4 HG over the first 2 cycles in both cohorts as per CTCAE v4.03. The secondary endpoints include PFS, overall response rate, time to progression, clinical benefit rate as per RECIST v1.1, and overall safety as per CTCAE 4.03. The stage II will be conducted if G3/4 HG after the first 2 cycles are observed in ≤3 pts of 23 in cohort A and ≤2 pts of 7 in cohort B. The final analysis will be defined as positive if ≤6 pts of 48 in cohort A and ≤4 pts of 20 in cohort B have G3/4 HG. The Simon two-stage design was planned to attain an 80% power at 5% nominal alpha level.

Clinical trial identification

NCT04300790.

Legal entity responsible for the study

MEDSIR.

Funding

Novartis.

Disclosure

A. Llombart Cussac: Leadership role: Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD; Shareholder/Stockholder/Stock options: MedSIR, Initia-Research; Advisory/Consultancy: Lilly, Roche, Pfizer, Novartis, Pierre Fabre, GenomicHealth, GSK; Speaker Bureau/Expert testimony: Lilly, AstraZeneca, MSD; Research grant/Funding (self): Roche, Foundation Medicine, Pierre Fabre, Agendia; Travel/Accommodation/Expenses: Roche, Lilly, Novartis, Pfizer, AstraZeneca. J.M. Pérez-Garcia: Advisory/Consultancy: Roche, Lilly; Travel/Accommodation/Expenses: Roche; Full/Part-time employment: MedSIR. A. Urruticoechea: Travel/Accommodation/Expenses: Roche/Genentech, Pfizer. J.F. Cueva Banuelos: Honoraria (self): Roche, AstraZeneca, Teva, Celgene, Novartis.; Advisory/Consultancy: Roche, AstraZeneca. J. Cortés: Advisory/Consultancy: Roche, Celgene, Cellestia, AstraZeneca, Biothera Pharmaceutical, Merus, Seattle Genetics, Daiichi Sankyo, Erytech, Athenex, Polyphor, Lilly, Servier, Merck Sharp & Dohme, GSK, Leuko, Bioasis, Clovis Oncology; Honoraria (self): Roche, Novartis, Celgene, Eisai, Pfizer, Samsung Bioepis, Lilly, Merck Sharp & Dohme, Daiichi Sankyo; Research grant/Funding (institution): Roche, Ariad Pharmaceuticals, AstraZeneca, Baxalta GMBH/Servier Affaires, Bayer Healthcare, Eisai, F. Hoffman-La Roche, Guardanth Health, Merck Sharp & Dohme, Pfizer, Piqur Therapeutics, Puma C, Queen Mary University of London; Licensing/Royalties: MedSIR. All other authors have declared no conflicts of interest.

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