What is the mechanism of action of this treatment?

Common treatments for breast cancer, such as PI3K inhibitors and estrogen receptor antagonists, work by targeting specific pathways crucial for cancer cell survival and proliferation. PI3K inhibitors, like Inavolisib, block the PI3K pathway, which is essential for cell growth and survival, thereby inhibiting cancer cell proliferation. Estrogen receptor antagonists, like Fulvestrant, bind to estrogen receptors on cancer cells, preventing estrogen from promoting tumor growth. These mechanisms are vital for hormone receptor-positive, HER2-negative breast cancer patients, as they help in effectively disrupting the cancer's growth and improving treatment outcomes.

What side effects are associated with this type of intervention?

Common treatments for breast cancer, particularly those involving PI3K inhibitors like Inavolisib and estrogen receptor antagonists like Fulvestrant, have known side effects. PI3K inhibitors can cause hyperglycemia, rash, diarrhea, and fatigue. Fulvestrant may lead to injection site reactions, hot flashes, fatigue, and nausea. Combining these treatments may result in overlapping toxicities, requiring careful management of side effects.

What prior FDA approvals exist?

The FDA has approved alpelisib, a PI3K inhibitor, in combination with fulvestrant for the treatment of hormone receptor-positive, HER2-negative, PIK3CA-mutated advanced breast cancer. This combination targets the PI3K pathway and estrogen receptors, similar to the investigational combination of Inavolisib plus Fulvestrant. Fulvestrant, an estrogen receptor antagonist, is also approved for use in various combinations for treating hormone receptor-positive metastatic breast cancer.

What other types of research exist?

Promising novel alternatives to Inavolisib plus Fulvestrant for breast cancer patients in 2024 include: 1) Alpelisib plus Fulvestrant, another PI3K inhibitor combined with an estrogen receptor antagonist, which has shown efficacy in similar patient populations. 2) CDK4/6 inhibitors such as Ribociclib, Palbociclib, or Abemaciclib in combination with endocrine therapy, which are already established but continue to show promise in ongoing studies. 3) Novel agents targeting the AKT pathway, such as Capivasertib, which are being investigated in combination with endocrine therapy. 4) Selective estrogen receptor degraders (SERDs) like Elacestrant, which offer a new approach to targeting estrogen receptors.

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PI3K Inhibitor

Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant for Breast Cancer (INAVO121 Trial)

Phase 3

Recruiting

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

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

Must have

Confirmation of biomarker eligibility: detection of specified mutation(s) of PIK3CA via specified test

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2

Must not have

Allergy or hypersensitivity to components or excipients of the inavolisib, fulvestrant, or alpelisib formulations

Investigational drug(s) within 4 weeks before randomization or within 5 half-lives of the investigational drug(s), whichever is longer

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomization until death due to any cause (up to approximately 85 months)

Awards & highlights

Summary

This trial compares two treatments for HR+/HER2-/PIK3CA-mutated mBC that failed CDK4/6i-based therapy.

Who is the study for?

This trial is for adults with HR-positive, HER2-negative, PIK3CA mutated advanced or metastatic breast cancer who've progressed after CDK4/6i and endocrine therapy. They should have a life expectancy over 6 months, an ECOG status of 0-2, and no more than two prior systemic therapies in the metastatic setting (one chemo allowed). Pre/perimenopausal women must be on LHRH agonist therapy.Check my eligibility

What is being tested?

The study compares the effectiveness and safety of Inavolisib plus Fulvestrant versus Alpelisib plus Fulvestrant in patients whose breast cancer has worsened despite previous treatments. It's a Phase III trial where participants are randomly assigned to one of these treatment combinations.See study design

What are the potential side effects?

Potential side effects include digestive issues, liver problems, blood sugar changes (especially important for diabetics), skin reactions like rashes or severe conditions such as Stevens-Johnson Syndrome, inflammation or infection risks including pneumonitis and eye inflammation.

Eligibility Criteria

Inclusion Criteria

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

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My cancer has a specific PIK3CA mutation.

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I can take care of myself and am up and about more than half of my waking hours.

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My breast cancer is advanced and cannot be removed by surgery or cured with radiation.

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My breast cancer is hormone-receptor positive and HER2-negative.

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My recommended treatment is hormone therapy, not chemotherapy.

Exclusion Criteria

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

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I am not allergic to inavolisib, fulvestrant, or alpelisib.

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I haven't taken any experimental drugs recently.

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I have had leptomeningeal disease or carcinomatous meningitis.

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I have Type 2 diabetes and am on treatment, or I have a history of Type 1 diabetes.

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I do not have conditions that affect how my body absorbs food.

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I cannot or do not want to swallow pills.

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I am currently suffering from jawbone decay.

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I do not have an active infection or have been hospitalized for one in the last week.

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I do not have severe liver problems, hepatitis, alcohol abuse, or cirrhosis.

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I have previously been treated with drugs targeting the PI3K/AKT/mTOR pathway for advanced cancer.

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I currently have active bowel inflammation.

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I have symptoms of lung problems, like trouble breathing.

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I take 10 mg or more of prednisone daily for a chronic condition.

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I have had eye inflammation or infections, or a history of uveitis related to autoimmune disease.

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I need extra oxygen every day.

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I have or had inflammatory bowel disease.

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My breast cancer is of a rare type called metaplastic.

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I don't have any eye conditions needing treatment that could affect my vision during the study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomization until death due to any cause (up to approximately 85 months)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomization until death due to any cause (up to approximately 85 months)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomization until death due to any cause (up to approximately 85 months) for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Blinded Independent Central Review (BICR)-Assessed Progression Free Survival (PFS)

Secondary outcome measures

BICR-Assessed Best Overall Response (BOR)

BICR-Assessed Clinical Benefit Rate (CBR)

BICR-Assessed Duration of Response (DOR)

+8 more

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Inavolisib + FulvestrantExperimental Treatment2 Interventions

Participants will be administered the treatments as outlined in the interventions section.

Group II: Alpelisib + FulvestrantActive Control2 Interventions

Participants will be administered the treatments as outlined in the interventions section.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Inavolisib

2021

Completed Phase 2

~260

Fulvestrant

2011

Completed Phase 3

~3810

0 / 23Eligibility 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

Common treatments for breast cancer, such as PI3K inhibitors and estrogen receptor antagonists, work by targeting specific pathways crucial for cancer cell survival and proliferation. PI3K inhibitors, like Inavolisib, block the PI3K pathway, which is essential for cell growth and survival, thereby inhibiting cancer cell proliferation. Estrogen receptor antagonists, like Fulvestrant, bind to estrogen receptors on cancer cells, preventing estrogen from promoting tumor growth. These mechanisms are vital for hormone receptor-positive, HER2-negative breast cancer patients, as they help in effectively disrupting the cancer's growth and improving treatment outcomes.

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.A Phase I Trial of BKM120 (Buparlisib) in Combination with Fulvestrant in Postmenopausal Women with Estrogen Receptor-Positive Metastatic Breast Cancer.