What side effects are associated with this type of intervention?

Common treatments for breast cancer, such as Alpelisib (a PI3K inhibitor) and Fulvestrant (an estrogen receptor antagonist), have specific side effects. Alpelisib is associated with hyperglycemia, rash, diarrhea, and decreased appetite. Fulvestrant can cause injection site pain, nausea, fatigue, and hot flashes. Other similar treatments, like different PI3K inhibitors, may also lead to gastrointestinal issues and liver enzyme abnormalities, while other estrogen receptor antagonists can cause menopausal symptoms and bone density loss. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate them effectively.

What prior FDA approvals exist?

The FDA has approved several treatments for hormone receptor-positive, HER2-negative advanced breast cancer that are similar to the combination of Alpelisib and Fulvestrant. Alpelisib, a PI3K inhibitor, is approved for use with Fulvestrant in patients with PIK3CA-mutated advanced breast cancer. Fulvestrant, an estrogen receptor antagonist, is also used in combination with other targeted therapies such as CDK4/6 inhibitors (e.g., Palbociclib, Ribociclib) to improve treatment outcomes. These combinations aim to inhibit cancer cell growth by targeting specific pathways involved in cell proliferation and hormone receptor signaling.

What other types of research exist?

Promising alternatives to Alpelisib and Fulvestrant for breast cancer treatment in 2024 include: 1) Trastuzumab Deruxtecan (Enhertu), an antibody-drug conjugate targeting HER2-positive breast cancer, 2) Sacituzumab Govitecan (Trodelvy), an antibody-drug conjugate for triple-negative breast cancer, and 3) Pembrolizumab (Keytruda), an immune checkpoint inhibitor for PD-L1 positive breast cancer. These therapies have shown significant efficacy in clinical trials and are expected to be important treatment options.

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PI3K Inhibitor

Alpelisib + Fulvestrant for Breast Cancer (EPIK-B5 Trial)

Phase 3

Recruiting

Research Sponsored by Novartis Pharmaceuticals

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant has HER2-negative breast cancer as defined by specific testing criteria

Participant has received ≤2 prior lines of systemic therapies overall in the metastatic setting, of which a maximum of 1 line of prior treatment with chemotherapy

Must not have

Participant has received prior treatment with specific inhibitors as listed

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the date of randomization up to maximum duration of 60 months

Awards & highlights

Pivotal Trial

Summary

This trial is testing whether a new drug combination of alpelisib and fulvestrant works better than just fulvestrant alone in men and postmenopausal women with a specific type of advanced breast cancer. Alpelisib targets cancer cell mutations, while fulvestrant blocks hormones that help the cancer grow.

Who is the study for?

This trial is for adults over 18 with HR-positive, HER2-negative advanced breast cancer who have progressed after treatment with an AI and a CDK4/6 inhibitor. They must have at least one measurable lesion, a PIK3CA mutation, and if female, be postmenopausal. They can't join if they've had more than two systemic therapies in the metastatic setting or prior treatment with certain inhibitors.

What is being tested?

The study tests the effectiveness of Alpelisib combined with Fulvestrant versus a placebo plus Fulvestrant in men or postmenopausal women whose advanced breast cancer has worsened despite previous treatments. The goal is to gather more data on this combination's safety and efficacy.

What are the potential side effects?

Alpelisib may cause high blood sugar levels, skin rash, diarrhea, nausea; while Fulvestrant can lead to injection site reactions, fatigue, nausea. Side effects vary by individual.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My breast cancer is not HER2 positive.

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I've had 2 or fewer treatments for my cancer, with only one being chemotherapy.

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I have at least one tumor that can be measured.

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My breast cancer is estrogen and/or progesterone receptor positive.

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My cancer came back or got worse after AI and CDK4/6 inhibitor therapy.

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My tumor has a PIK3CA mutation.

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I am a woman and have gone through menopause.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have been treated with specific inhibitors before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the date of randomization up to maximum duration of 60 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the date of randomization up to maximum duration of 60 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from the date of randomization up to maximum duration of 60 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free survival (PFS) based on BIRC assessments and using RECIST v1.1 criteria

Secondary study objectives

Change from baseline in global health status/QoL and symptom scale scores of the EORTC QLQ-C30

Clinical benefit rate (CBR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria

Duration of response (DOR) with confirmed response based on BIRC assessments and using RECIST v1.1 criteria

+7 more

Side effects data

From 2023 Phase 3 trial • 572 Patients • NCT02437318

62%

Hyperglycaemia

57%

Diarrhoea

45%

Nausea

35%

Rash

35%

Decreased appetite

26%

Vomiting

26%

Weight decreased

24%

Fatigue

24%

Stomatitis

20%

Asthenia

20%

Alopecia

18%

Mucosal inflammation

18%

Pruritus

17%

Dysgeusia

17%

Headache

15%

Dry skin

14%

Oedema peripheral

14%

Pyrexia

14%

Back pain

13%

Rash maculo-papular

11%

Dyspepsia

11%

Abdominal pain

11%

Arthralgia

10%

Dry mouth

10%

Urinary tract infection

10%

Blood creatinine increased

10%

Gamma-glutamyltransferase increased

10%

Aspartate aminotransferase increased

10%

Cough

Nasopharyngitis

Pain in extremity

Dizziness

Hypertension

Anaemia

Constipation

Alanine aminotransferase increased

Hypokalaemia

Dyspnoea

Myalgia

Muscle spasms

Insomnia

Lipase increased

Abdominal pain upper

Lymphoedema

Musculoskeletal pain

Erythema

Upper respiratory tract infection

Bone pain

Hot flush

Osteonecrosis of jaw

Acute kidney injury

Pneumonitis

Pulmonary embolism

Dehydration

Upper gastrointestinal haemorrhage

General physical health deterioration

Cellulitis

Pleural effusion

Hypersensitivity

Pneumonia

Hyponatraemia

Muscular weakness

Brain oedema

Renal failure

Erythema multiforme

100%

80%

60%

40%

20%

Study treatment Arm

Placebo qd + Fulvestrant

Alpelisib qd + Fulvestrant

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: Alpelisib plus fulvestrantExperimental Treatment2 Interventions

Alpelisib 300 mg orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15, and on Day 1 on every Cycle thereafter, in a 28 days cycle.

Group II: Alpelisib-matching placebo plus fulvestrantPlacebo Group2 Interventions

Alpelisib-matching placebo orally once daily on a continuous dosing schedule, in a 28-day cycle + fulvestrant 500 mg as intramuscular injection on Cycle 1 Day 1 and 15 and on Day 1 on every Cycle thereafter, in a 28 days cycle. Participants who have disease progression per RECIST v1.1 as assessed by BIRC will have the option to crossover to be treated with alpelisib plus fulvestrant

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Alpelisib

2018

Completed Phase 3

~960

Fulvestrant

2011

Completed Phase 3

~3510

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Alpelisib is a PI3K inhibitor that targets the PI3K pathway, which is often mutated in breast cancer, leading to uncontrolled cell growth and survival. By inhibiting this pathway, Alpelisib can reduce tumor growth and proliferation. Fulvestrant is an estrogen receptor antagonist that binds to estrogen receptors on cancer cells, leading to their degradation and preventing estrogen from promoting cancer cell growth. These mechanisms are crucial for breast cancer patients as they directly target the pathways and receptors that drive cancer progression, offering a more tailored and potentially effective treatment approach. Other common treatments include CDK4/6 inhibitors, which block proteins involved in cell division, and aromatase inhibitors, which reduce estrogen production, further hindering cancer cell growth.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Alpelisib for the treatment of PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer.An evidence-based review of the outcome of fulvestrant plus a targeted agent versus fulvestrant alone in treating hormone receptor-positive endocrine therapy-resistant metastatic breast cancer.