Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant for Breast Cancer (INAVO121 Trial)
Recruiting in Palo Alto (17 mi)
+275 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Waitlist Available
Sponsor: Hoffmann-La Roche
No Placebo Group
Pivotal Trial (Near Approval)
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This trial is testing two drug combinations to find out which one is better for treating a specific type of advanced breast cancer that hasn't responded to previous treatments. The drugs work by stopping cancer cells from growing and spreading.
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, if you are on Type 2 diabetes medication, you cannot participate. Also, you cannot be on chronic therapy of 10 mg or more of prednisone per day or an equivalent dose of other corticosteroids or immunosuppressants.
What data supports the idea that Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant for Breast Cancer is an effective drug?
The available research shows that Alpelisib combined with Fulvestrant is effective for treating a specific type of breast cancer. In studies, patients with a certain genetic mutation (PIK3CA) who took Alpelisib and Fulvestrant had a longer time before their cancer got worse compared to those who did not take Alpelisib. For example, in one study, the time before the cancer progressed was about 11 months for those on Alpelisib and Fulvestrant, compared to about 5.7 months for those who did not take Alpelisib. However, there is no specific data provided on Inavolisib combined with Fulvestrant, so we cannot compare its effectiveness directly to Alpelisib combined with Fulvestrant based on the information available.
12345What safety data is available for the treatment of Inavolisib + Fulvestrant vs Alpelisib + Fulvestrant for breast cancer?
The safety data for Alpelisib (Piqray) combined with Fulvestrant (Faslodex) in treating PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer includes findings from several studies. The SOLAR-1 trial showed that common adverse reactions were increased glucose, increased creatinine, diarrhea, rash, decreased lymphocyte count, increased gamma glutamyl transferase, nausea, increased alanine aminotransferase, fatigue, decreased hemoglobin, increased lipase, decreased appetite, stomatitis, vomiting, decreased weight, decreased calcium, decreased glucose, prolonged activated partial thromboplastin time, and alopecia. In the French early access program, 39.1% of patients discontinued Alpelisib due to adverse events. The safety profile of Alpelisib requires careful patient selection and monitoring, especially regarding baseline glycemic status, due to the risk of hyperglycemia. No specific safety data for Inavolisib combined with Fulvestrant was provided in the research.
12356Is the drug Alpelisib, Fulvestrant, Inavolisib a promising treatment for breast cancer?
Yes, the drug combination of Alpelisib and Fulvestrant is promising for treating a specific type of breast cancer. It has been shown to help patients with hormone receptor-positive, HER2-negative breast cancer that has a PIK3CA mutation. Studies have shown that it can extend the time patients live without the cancer getting worse.
12357Eligibility Criteria
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.Inclusion Criteria
My cancer has a specific PIK3CA mutation.
I can take care of myself and am up and about more than half of my waking hours.
My breast cancer is advanced and cannot be removed by surgery or cured with radiation.
My breast cancer is hormone-receptor positive and HER2-negative.
My recommended treatment is hormone therapy, not chemotherapy.
Exclusion Criteria
I am not allergic to inavolisib, fulvestrant, or alpelisib.
I haven't taken any experimental drugs recently.
I have had leptomeningeal disease or carcinomatous meningitis.
I have Type 2 diabetes and am on treatment, or I have a history of Type 1 diabetes.
I do not have conditions that affect how my body absorbs food.
I cannot or do not want to swallow pills.
I am currently suffering from jawbone decay.
I do not have an active infection or have been hospitalized for one in the last week.
I do not have severe liver problems, hepatitis, alcohol abuse, or cirrhosis.
I have previously been treated with drugs targeting the PI3K/AKT/mTOR pathway for advanced cancer.
I currently have active bowel inflammation.
I have symptoms of lung problems, like trouble breathing.
I take 10 mg or more of prednisone daily for a chronic condition.
I have had eye inflammation or infections, or a history of uveitis related to autoimmune disease.
I need extra oxygen every day.
I have or had inflammatory bowel disease.
My breast cancer is of a rare type called metaplastic.
I don't have any eye conditions needing treatment that could affect my vision during the study.
Participant Groups
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.
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.
Alpelisib is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Piqray for:
- Hormone receptor-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer following progression on or after an endocrine-based regimen
🇪🇺 Approved in European Union as Piqray for:
- Hormone receptor-positive, HER2-negative, PIK3CA-mutated, locally advanced or metastatic breast cancer in combination with fulvestrant
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
CIUSSS de l'Est-de-l'Ile-de-Montréal - Hôpital Maisonneuve-RosemontMontreal, Canada
Cancer Care Centers of BrevardPalm Bay, FL
Texas Tech University Health Sciences CenterEl Paso, TX
Arthur J.E. Child Comprehensive Cancer Center-CalgaryCalgary, Canada
More Trial Locations
Loading ...
Who is running the clinical trial?
Hoffmann-La RocheLead Sponsor
References
Incidence, risk factors, and management of alpelisib-associated hyperglycemia in metastatic breast cancer. [2023]The combination of fulvestrant with alpelisib, a PI3K inhibitor, improves progression-free survival in metastatic hormone receptor-positive, PIK3CA-mutant breast cancer. This study describes the incidence, risk factors, and treatment of alpelisib-associated hyperglycemia.
Alpelisib and fulvestrant in PIK3CA-mutated hormone receptor-positive HER2-negative advanced breast cancer included in the French early access program. [2023]SOLAR-1 and BYLieve trials documented the efficacy of the PI3K-inhibitor alpelisib in pre-treated PIK3CA-mutant, hormone receptor-positive, HER2-negative (HR+/HER2-) advanced breast cancer (ABC) patients. We report here real-life data of patients prospectively registered in the French alpelisib early access program (EAP) opened to PIK3CA-mutant HR+/HER2- ABC patients treated with alpelisib and fulvestrant. Primary endpoint was PFS by local investigators using RECIST1.1. Eleven centers provided individual data on 233 consecutive patients. Patients had received a median number of 4 (range: 1-16) prior systemic treatments for ABC, including CDK4/6 inhibitor, chemotherapy, fulvestrant and everolimus in 227 (97.4%), 180 (77.3%), 175 (75.1%) and 131 (56.2%) patients, respectively. After a median follow-up of 7.1 months and 168 events, median PFS was 5.3 months (95% CI: 4.7-6.0). Among 186 evaluable patients, CBR at 6 months was 45.3% (95% CI: 37.8-52.8). In multivariable analysis, characteristics significantly associated with a shorter PFS were age 5 lines of prior treatments (HR = 1.4, 95% CI = 1.0-2.0) and the C420R PI3KCA mutation (HR = 4.1, 95% CI = 1.3-13.6). N = 91 (39.1%) patients discontinued alpelisib due to adverse events. To our knowledge, this is the largest real-life assessment of alpelisib efficacy. Despite heavy pre-treatments, patients derived a clinically relevant benefit from alpelisib and fulvestrant.
Alpelisib: First Global Approval. [2020]Alpelisib (Piqray™)-an orally available phosphatidylinositol 3-kinase (PI3K) inhibitor with specific activity against PI3K alpha (PI3Kα)-is being developed by Novartis for the treatment of breast cancer. Alpelisib has demonstrated efficacy in combination with fulvestrant as treatment for hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer in patients with a PIK3CA mutation and was recently approved for this indication in the USA. This article summarizes the milestones in the development of alpelisib leading to this first approval.
Alpelisib in the treatment of metastatic HR+ breast cancer with PIK3CA mutations. [2021]Since the US FDA approval of everolimus/exemestane in July 2012, and of the first CDK 4/6 inhibitor, palbociclib, combined with endocrine treatment in February 2015, a third class of therapeutic compounds, the PI3K inhibitors, has been introduced to the arsenal of targeted therapies overcoming endocrine resistance in hormone receptor-positive metastatic breast cancer. Alpelisib (PIQRAY®) is the first of these novel agents yielding promising clinical results, giving an impetus to further development of tailored endocrine anticancer treatments. Herein, we review its pharmacodynamic and pharmacokinetic properties, safety and efficacy data, as well as Phase III SOLAR-1 trial, prompting FDA approval of alpelisib in hormone receptor-positive metastatic breast cancer harboring PIK3CA mutations. Furthermore, implications for clinical use and current research will also be discussed.
FDA Approval Summary: Alpelisib Plus Fulvestrant for Patients with HR-positive, HER2-negative, PIK3CA-mutated, Advanced or Metastatic Breast Cancer. [2022]On May 24, 2019, the FDA granted regular approval to alpelisib in combination with fulvestrant for postmenopausal women, and men, with hormone receptor (HR)-positive, HER2-negative, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutated, advanced or metastatic breast cancer as detected by an FDA-approved test following progression on or after an endocrine-based regimen. Approval was based on the SOLAR-1 study, a randomized, double-blind, placebo-controlled trial of alpelisib plus fulvestrant versus placebo plus fulvestrant. The primary endpoint was investigator-assessed progression-free survival (PFS) per RECIST v1.1 in the cohort of trial participants whose tumors had a PIK3CA mutation. The estimated median PFS by investigator assessment in the alpelisib plus fulvestrant arm was 11 months [95% confidence interval (CI), 7.5-14.5] compared with 5.7 months (95% CI, 3.7-7.4) in the placebo plus fulvestrant arm (HR, 0.65; 95% CI, 0.50-0.85; two-sided P = 0.001). The median overall survival was not yet reached for the alpelisib plus fulvestrant arm (95% CI, 28.1-NE) and was 26.9 months (95% CI, 21.9-NE) for the fulvestrant control arm. No PFS benefit was observed in trial participants whose tumors did not have a PIK3CA mutation (HR, 0.85; 95% CI, 0.58-1.25). The most common adverse reactions, including laboratory abnormalities, on the alpelisib plus fulvestrant arm were increased glucose, increased creatinine, diarrhea, rash, decreased lymphocyte count, increased gamma glutamyl transferase, nausea, increased alanine aminotransferase, fatigue, decreased hemoglobin, increased lipase, decreased appetite, stomatitis, vomiting, decreased weight, decreased calcium, decreased glucose, prolonged activated partial thromboplastin time, and alopecia.
Alpelisib for the treatment of PIK3CA-mutated, hormone receptor-positive, HER2-negative metastatic breast cancer. [2021]Introduction: Two-thirds of advanced breast cancers are hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-). Gene mutations in PIK3CA, encoding the PI3K catalytic subunit alpha of phosphatidyl-inositol 3-kinase (PI3K), are a frequent event in this population and are implicated in hormone therapy resistance. Alpelisib is a PI3K-alpha inhibitor and is the first PI3K inhibitor approved, in association with fulvestrant, by the FDA and EMA, based on improved progression-free survival (PFS) versus fulvestrant alone in a randomized phase III trial in HR+/HER2-, PIK3CA-mutated tumors following progression on/after HT.Areas covered: The scientific rationale, preclinical development, pharmacokinetics, and clinical efficacy/safety of alpelisib-fulvestrant are summarized. The role of alpelisib in the clinical setting is discussed, referencing current therapeutic options and clinical challenges associated with alpelisib's safety profile.Expert opinion: Alpelisib is an option for patients with HR+/HER2-, PIK3CA-mutated tumors whose disease progressed during/after aromatase inhibitor treatment. The PFS benefit appears clinically significant over fulvestrant alone, with a 7.9 months, non-significant, improvement in overall survival. Its safety profile requires strict patient selection, mainly based on baseline glycemic status, and close monitoring.
The efficacy and safety of alpelisib in breast cancer: A real-world analysis. [2023]Published trials of alpelisib + fulvestrant demonstrate efficacy and high rates of adverse effects as a first-line treatment option for metastatic breast cancer and as an option after cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i). The purpose of this analysis is to determine the real-world efficacy and safety of this regimen in heavily pretreated patients. This is a retrospective cohort analysis evaluating patients receiving alpelisib + fulvestrant for hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer who previously received ≤ 2 lines of therapy in the metastatic setting and those who previously received ≥ 3 lines of therapy in the metastatic setting. Adverse effects, specifically hyperglycemia, rash, and diarrhea, were reported for the entire population. Thirty-three patients were included in this analysis. Progression-free survival (PFS), overall survival, time to change in therapy, and time to discontinuation were similar in the two groups. Forty-nine percent of patients discontinued alpelisib + fulvestrant due to progression of disease, and 27% of patients discontinued treatment due to adverse effects. Hyperglycemia, rash, and diarrhea occurred at high rates: 66.7%, 45.5%, and 72.7%, respectively. All three of these adverse effects required hospitalizations and pharmacological treatment. This analysis demonstrates that the outcomes of alpelisib + fulvestrant were worse in the real-world salvage setting in HR+, HER2- metastatic breast cancer as compared to the front-line setting. The real-world tolerability of this regimen is still of great concern.