A NIS of Alpelisib in Combination With Fulvestrant in Postmenopausal Women, and Men, With HR+,HER2- , Locally Advanced or Metastatic Breast Cancer With a PIK3CA Mutation, After Disease Progression Following Endocrine Therapy as Monotherapy, in the Real-world Setting

Alpelisib (Piqray®) Post-Authorization Safety Study (PASS): a Non-interventional Study of Alpelisib in Combination With Fulvestrant in Postmenopausal Women, and Men, With Hormone Receptor Positive (HR+), Human Epidermal Growth Factor Receptor 2 Negative (HER2-), Locally Advanced or Metastatic Breast Cancer With a Phosphatidylinositol-3-kinase Catalytic Subunit Alpha (PIK3CA) Mutation, After Disease Progression Following Endocrine Therapy as Monotherapy, in the Real-world Setting

This was a prospective, multi-national, non-interventional study (NIS) collecting data from postmenopausal women, and adult men, with HR+, HER2- locally advanced or metastatic breast cancer whose tumor harbors a PIK3CA mutation, and who were to be treated with alpelisib in combination with fulvestrant after disease progression following endocrine therapy as monotherapy, in the real-world setting.

Study Overview

• Status: Terminated
• Conditions: Hormone Receptor Positive HER2 Negative Breast Cancer With a PIK3CA Mutation
• Intervention / Treatment: Other: Alpelisib; Other: Fulvestrant

Detailed Description

Once the patient provided informed consent, he or she was enrolled in the study. Patients were planned to be followed from enrollment until 1) 30 days after alpelisib treatment discontinuation, or 2) death, or 3) lost to follow-up, or 4) patient withdrawal, or 5) physician decision to end treatment/study, or 6) end of the study, whichever occured first. The end of the study was defined as a maximum of 12 months after the date the last patient was enrolled (LPFV); if the last patient was still on treatment on that date, they were not be followed up any further.

Due to very low patient numbers (4 patients, including 2 eligible patients) no statistical analyses were performed. Database lock was achieved without all queries resolved.

• Study Type: Observational
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70124
    • Novartis Investigative Site
  • Potenza, Italy, 85100
    • Novartis Investigative Site
  • PV
    • Pavia, PV, Italy, 27100
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Postmenopausal women, and adult men, with HR+, HER2- locally advanced or metastatic breast cancer whose tumor harbors a PIK3CA mutation, and who were treated with alpelisib in combination with fulvestrant after disease progression following endocrine therapy as monotherapy, in the real-world setting.

Description

Inclusion Criteria:

• Signed informed consent from the patient or a legally acceptable representative, obtained before any study-related activities are undertaken
• Patients diagnosed with HR+, HER2- locally advanced or metastatic breast cancer with a PIK3CA mutation
• Patients who have disease progression following endocrine therapy as monotherapy
• Patients must be postmenopausal women, or men, ≥18 years of age
• Patients recruited on or before their first prescribed dose of alpelisib in combination with fulvestrant

Exclusion Criteria:

• Use of alpelisib prior to signing the informed consent form for this study
• Participation in an interventional study within 30 days prior to the initiation of alpelisib

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

alpelisib in combination with fulvestrant; Patients treated with alpelisib in combination with fulvestrant

Other: Alpelisib; Prospective observational PASS study. There was no treatment allocation. Patients recruited on or before their first prescribed dose of alpelisib in combination with fulvestrant were enrolled.; Other: Fulvestrant; Prospective observational PASS study. There was no treatment allocation. Patients recruited on or before their first prescribed dose of alpelisib in combination with fulvestrant were enrolled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence proportion of hyperglycemia	To assess the incidence of hyperglycemia (Adverse Event of Special Iinterest) observed during follow-up of patients treated with alpelisib in combination with fulvestrant.	Up to 53 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Calculated BMI	Calculated BMI will be collected	Baseline
Medical history	Number of patients with diabetes mellitus (including gestational diabetes), tobacco use, baseline diabetic status per laboratory values for HbA1c and FPG	Baseline
Family history of diabetes mellitus	Yes/ No variable	Baseline
Number of patients with concomitant medications known to affect blood glucose levels	Number of patients with concomitant medications known to affect blood glucose levels will be measured	Baseline
Number of participants with incidence proportion of ketoacidosis and Hyperglycemic Hyperosmolar Non-Ketotic Syndrome (HHNKS)	Number of participants with incidence proportion of ketoacidosis and HHNKS based on AE data	Up to 53 months
Incidence of the Adverse Events of Special Interest (AESI) of Osteonecrosis of the Jaw (ONJ)	Incidence of AESI of Osteonecrosis of the Jaw (ONJ) will be provided	Up to 53 months
Number of participants with risk factors for Osteonecrosis of the Jaw (ONJ) observed	Number of participants with risk factors for ONJ will be collected. Risk factors for ONJ include: Patient characteristics: age, calculated BMI, sex; Prior and/or concomitant use of bisphosphonates (e.g. zoledronic acid).; Prior and/or concomitant use of RANKligand inhibitors (e.g. denosumab).	Baseline
Incidence proportion of AESIs	The incidence proportion of AESIs: GI toxicity (nausea, vomiting and diarrhea); Rash; Hypersensitivity (e.g. anaphylactic reaction); Pancreatitis; Pneumonitis; SCARs	Up to 53 months
Other safety and tolerability events	The incidence proportion of: AEs; AEs leading to dose interruptions; AEs leading to dose reductions; AEs leading to permanent discontinuation of alpelisib in combination with fulvestrant; SAEs	Up to 53 months
Number of patients with hematological and biochemical laboratory abnormalities	Number of patients with hematological and biochemical laboratory abnormalities will be provided	Up to 53 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Link to study results

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2023
• Primary Completion (Actual): October 18, 2024
• Study Completion (Actual): October 18, 2024

Study Registration Dates

• First Submitted: July 8, 2021
• First Submitted That Met QC Criteria: July 8, 2021
• First Posted (Actual): July 19, 2021

Study Record Updates

• Last Update Posted (Estimated): December 4, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Breast Cancer; non-interventional study; NIS; PASS; fulvestrant; alpelisib
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Fulvestrant; Alpelisib
• Other Study ID Numbers: CBYL719C2404

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO