J. Cortes Castan (Barcelona, Spain)
Vall d'Hebron University HospitalAuthor Of 4 Presentations
Potential new drugs with activity in metastatic TNBC (ID 287)
Medical need to improve on standard therapies for HR+/HER2- EBC (ID 334)
Review of recent data with IO + Chemo (ID 330)
Individualizing therapeutic decision-making for patients with HR+/HER2- EBC (ID 337)
Presenter Of 4 Presentations
Potential new drugs with activity in metastatic TNBC (ID 287)
Medical need to improve on standard therapies for HR+/HER2- EBC (ID 334)
Review of recent data with IO + Chemo (ID 330)
Individualizing therapeutic decision-making for patients with HR+/HER2- EBC (ID 337)
Moderator Of 2 Sessions
Author Of 2 Presentations
- A. Llombart (Valencia, Spain)
- J. Pérez-Garcia (Barcelona, Spain)
- S. Blanch (Valencia, Spain)
- P. Tolosa (Madrid, Spain)
- M. Ruiz Borrego (Seville, Spain)
- M. Gion Cortes (Madrid, Spain)
- A. Fernádez (Hospitalet de Llobregat, Spain)
- A. Urruticoechea (Donostia, Spain)
- E. Galve (Bilbao, Spain)
- J. Cueva Banuelos (Santiago de Compostela, La, Spain)
- J. Ponce (Hospital General Universitario de Alicante, Spain)
- J. Alonso (El Palmar, Spain)
- M. Capelán (Barcelona, Spain)
- E. Martínez (Castellón de la Plana, Spain)
- B. Bermejo De Las Heras (Valencia, Va, Spain)
- B. Rojas (Madrid, Spain)
- T. Martos (Barcelona, Spain)
- A. López (León, Spain)
- F. Gómez-Peralta (Segovia, Spain)
- J. Cortes Castan (Barcelona, Spain)
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
Abstract
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.
- E. Ciruelos (Madrid, Spain)
- J. Ponce (Hospital General Universitario de Alicante, Spain)
- J. Cortes Castan (Barcelona, Spain)
- S. Pernas Simon (Hospitalet de Llobregat, Spain)
- E. Garate (Bilbao, Spain)
- M. Melé (Reus, Spain)
- Á. Montaño (Sevilla, Spain)
- N. Martinez-Jañez (Madrid, Spain)
- M. Oliveira (Barcelona, Spain)
- J. De la Haba-Rodríguez (Córdoba, Spain)
- E. Vega (Madrid, Spain)
- A. Perello Martorell (Palma de Mallorca, Spain)
- B. Bermejo De Las Heras (Valencia, Va, Spain)
- B. Cantos Sanchez De Ibarguen (Majadahonda, Spain)
- E. Martínez (Castellón de la Plana, Spain)
- E. Vila Navarro (Barcelona, Spain)
- T. Pascual (Barcelona, Spain)
- X. González-Farré (Sant Cugat del Vallés, Spain)
- P. Villagrasa (Barcelona, Spain)
- A. Prat (Barcelona, Spain)
130TiP - SOLTI-1303 PATRICIA II randomized phase II trial of palbociclib plus trastuzumab and endocrine therapy (ET) versus treatment of physician's choice (TPC) in metastatic HER2-positive and hormone receptor-positive (HER2+/HR+) breast cancer (BC) with PAM50 luminal intrinsic subtype
Abstract
Background
PATRICIA phase II trial showed that Palbociclib in combination with trastuzumab is safe and exhibits promising survival outcomes in trastuzumab pretreated HER2+/HR+ advanced breast cancer with a PAM50 Luminal A or B subtype (Ciruelos E. et al, CCR 2020). Based on these results, PATRICIA II was designed to include only patients with HER2+/HR+, PAM50 Luminal A/B tumors to receive palbociclib, trastuzumab and ET versus treatment of physician’s choice (TPC).
Trial design
PATRICIA II is a randomized open-label, adaptive design, phase II study. Patients must have centrally confirmed HER2+/HR+ and PAM50 Luminal A or B tumors and have received at least 1 (and no more than 4) prior lines of anti-HER2 regimens for locally advanced or metastatic BC. Patients are randomized 1:1 to receive trastuzumab plus palbociclib at a standard dose of 125 mg/day orally 3 weeks on/ 1 week off and ET (Cohort C1) or TPC (cohort C2). ET options in cohort 1 are either an aromatase inhibitor, fulvestrant or tamoxifen +/- ovarian suppression. TPC options in cohort C2 are T-DM1 or chemotherapy (gemcitabine, vinorelbine, capecitabine, eribulin, paclitaxel or docetaxel) plus trastuzumab. Stratification factors include number of previous regimens for advanced or metastatic BC (1-2 vs 3-4) and the presence of visceral disease (yes vs no). Primary endpoint is to compare the progression-free survival between two arms. The study has an 80% power with two-sided alpha=0.05 to detect a HR of 0.62 in favor of the palbociclib cohort. Secondary endpoints include response rate, overall survival, safety, and quality of life. Tumor tissue and blood samples will be collected for biomarker analyses. An estimated total of 516 patients will be screened to include 232 patients with HER2+/HR+ PAM50 Luminal A or B tumors. The recruitment is ongoing in 20 sites in Spain and as of February 3rd, 2021, 107 patients were screened and 30 were enrolled in the trial.
Clinical trial identification
NCT02448420.
Legal entity responsible for the study
SOLTI.
Funding
Pfizer.
Disclosure
E.M. Ciruelos: Advisory/Consultancy, Non-remunerated activity/ies: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Lilly; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Novartis; Advisory/Consultancy: MSD. S. Pernas Simon: Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Polyphor; Advisory/Consultancy: Seattle Genetics; Advisory/Consultancy: Roche. M. Oliveira: Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Philips Healthcare; Advisory/Consultancy, Research grant/Funding (institution): Genentech; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Roche; Research grant/Funding (institution): Immunomedics; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Seattle Genetics; Advisory/Consultancy, Research grant/Funding (institution): GSK; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution): Zenith Epigenetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy: Puma Biotechnology; Travel/Accommodation/Expenses: Pierre Fabre; Travel/Accommodation/Expenses: Eisai. B. Bermejo De Las Heras: Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy: Palex; Advisory/Consultancy: MSD; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pfizer. X. González-Farré: Advisory/Consultancy: SOLTI Breast Cancer Group; Advisory/Consultancy, Non-remunerated activity/ies: Roche; Advisory/Consultancy: Eisai. P. Villagrasa: Honoraria (self): NanoString. A. Prat: Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self): Roche; Honoraria (self), Advisory/Consultancy: MSD Oncology; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Daiichi Sankyo; Advisory/Consultancy, Research grant/Funding (self): NanoString Technologies; Advisory/Consultancy: Oncolytics Biotech; Advisory/Consultancy: Amgen; Advisory/Consultancy: Puma. All other authors have declared no conflicts of interest.