ESMO Breast is a 4-day European multidisciplinary event, conceived to gather researchers and clinicians working on breast cancer, also including insights into translational research, new therapeutic approaches, biomarkers research and molecular diagnostics.
MEDSIR is pleased to participate with the poster “Metformin in the Prevention of Hyperglycemia in Patients with PIK3CA-mutated, Hormone Receptor (HR)[+]/HER2[–] Advanced Breast Cancer Treated with Alpelisib plus Fulvestrant: METALLICA Study”, presented by its main author Dr. Antonio Llombart-Cussac, Head of the Medical Oncology Service at Hospital Arnau de Vilanova. In this poster, Dr. Llombart will be reporting the study design and the initial findings from the study.
METALLICA is a prospective, multicenter, open label, Simon’s-two stage design, phase II trial involving patients with a hormone receptor–positive (HR+) / human epidermal growth factor receptor 2–negative (HER2–) / PI3K catalytic subunits p110α (PIK3CA) mutated (PIK3CAMut) advanced breast cancer (ABC), who previously received at least one treatment with an aromatase inhibitor (AI). The study aims at assessing the effect of metformin in the prevention of hyperglycemia (HG) in luminal ABC patients treated with alpelisib plus endocrine therapy.
Mutations in the enzyme PI3K, leading to the constitutive activation of its pathway, are recognized as inducers of resistance to ET in HR+ ABC. The combination of fulvestrant plus alpelisib showed an increased clinical benefit in patients with luminal ABC PI3KCAMut. Despite a generally acceptable safety profile, alpelisib is generally distinguished by the onset of HG, directly related to on-target PI3K inhibition. HG can be managed with the administration of metformin, a first line medication for the treatment of type-2 diabetes, which has also demonstrated antitumorigenic efficacy.
“The combination of alpelisib with fulvestrant has shown impressive activity as second line therapy in PIK3CAMut ABC patients. Hyperglycemia is the most common adverse event that leads to treatment discontinuation, thus requiring the introduction of proactive and effective measures”, affirmed Dr. Llombart, main author of the communication.
In METALLICA, a total of 68 PIK3CAMut mutated patients will be accrued through multiple institution in Spain into two study cohorts, divided according to their glycemia status at baseline: (A) 48 pts with fasting glycemia <100 mg/dL and glycosylated hemoglobin (HbA1c) < 5.7%; (B) 20 pts with fasting glycemia 100–140 mg/dL and/or HbA1c 5.7–6.4%. All the patients will receive the combination of metformin, fulvestrant, and alpelisib until progression of disease or unacceptable toxicity, with the primary objective of assessing the rate of grade 3-grade 4 (G3-G4) HG over the first 2 cycles of treatment. Evaluation of efficacy in terms of progression-free survival, overall response rate, time to progression, clinical benefit rate will be the secondary objective of the study.
Today, METALLICA is open for recruitment, with 16 patients already enrolled in the ongoing stage I of the study. The stage II will be conducted if G3-G4 HG after the first 2 cycles will be observed in ≤3 patients of 23 in cohort A, and ≤2 patients 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.
If successful, METALLICA will contribute to improve the management of HR+ PIK3CAMut ABC and be beneficial in the control of adverse events related to alpelisib administration.
The METALLICA study is funded by Novartis, and entirely sponsored and designed by MEDSIR.
This communication will be available online during the time span of the ESMO Breast congress, join us!