Table of Contents

• Breast cancer studies
• Rare disease studies
• Trial design, phases, and who can join
• Main endpoints and what they mean
• Comparisons with other treatments
• Safety focus in the trials

Breast cancer studies

Many Alpelisib trials study advanced breast cancer, especially hormone receptor-positive and HER2-negative disease.^[1][2][4]

Several studies include patients with a PIK3CA mutation, which means the cancer has a specific gene change used to choose treatment groups.^[1][5]

Some trials test Alpelisib with endocrine therapy such as fulvestrant or letrozole, while others compare Alpelisib-based treatment with placebo or with other medicines.^[1][4][7]

One completed Phase 3 study looked at Alpelisib plus olaparib in platinum-resistant or refractory high-grade serous ovarian cancer, but this was not a breast cancer study.^[3]

Rare disease studies

Alpelisib is also being studied in rare conditions linked to PIK3CA changes, including PIK3CA-related overgrowth spectrum (PROS), Megalencephaly-CApillary malformation Polymicrogyria syndrome (MCAP), lymphatic malformations, and Dent 2 disease.^[5][6][8][9]

These studies include both children and adults in some trials, showing that the research is not limited to one age group.^[5][6]

Some rare disease studies look at scan-based response, while others focus on long-term safety or changes in daily function.^[5][8][9]

Trial design, phases, and who can join

The trial list includes Phase 1, Phase 2, Phase 3, and Phase 4 studies, which means Alpelisib is being studied at different stages of research.^{[1][2][4][5][8]}

Some trials are randomized, which means participants are assigned to different groups by chance, and some are single-arm studies, which means everyone receives the study treatment.^[2][5][8]

Who can join depends on the study. The listed trials include adults with advanced or metastatic breast cancer, men and postmenopausal women in one study, and children, adolescents, and adults in some rare disease studies.^{[1][2][4][5][6][8]}

Some studies also require prior treatment, such as a previous CDK4/6 inhibitor, aromatase inhibitor, or endocrine therapy before joining.^[2][4][10]

Main endpoints and what they mean

Many trials measure progression-free survival (PFS), which is the time before the disease gets worse or the patient dies from any cause.^{[3][4][7][10][11]}

Some studies measure objective response, meaning a clear improvement on scans, such as a reduction in tumor or lesion size.^[3][5][8][9]

Other endpoints include the rate of hyperglycemia, which means high blood sugar, and the rate of treatment stopping because of related side effects.^[1][2]

In rare disease studies, endpoints may include MRI changes, kidney uptake of a tracer, or scores on a behavior scale used to measure daily function.^[5][8][9]

Comparisons with other treatments

Several trials compare Alpelisib with other treatment options rather than testing it alone.^{[2][4][7][11]}

Examples include Alpelisib plus fulvestrant versus placebo plus fulvestrant, Alpelisib plus trastuzumab-based treatment versus trastuzumab plus chemotherapy, and Alpelisib plus olaparib versus cytotoxic chemotherapy in ovarian cancer.^[3][4][7]

One study also compares Alpelisib plus fulvestrant with another targeted treatment combination, inavolisib plus fulvestrant, using blinded central review of scans.^[7]

Safety focus in the trials

Safety is a major part of the Alpelisib research program, especially in breast cancer studies where hyperglycemia is closely tracked.^[1][2]

One study looks at whether metformin can help prevent high blood sugar in patients taking Alpelisib plus endocrine therapy.^[1]

Another study tests whether taking Alpelisib at a different time of day, with fasting and a low carbohydrate diet, may change toxicity and efficacy.^[2]

Other trials measure general side effects, serious adverse events, dose changes, and whether treatment must be stopped because of related problems.^[4][5][8][9]