Anastrozole + Palbociclib for Breast Cancer

Overseen By Wendy L Vandermolen, RN

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Antoinette Tan, MD

Must be taking: LHRH agonists

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: CNS metastases, Cardiac issues, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 4 years or until disease progression, unacceptable toxicity, participant withdrawal, or investigator decision

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, anastrozole (Arimidex) and palbociclib (Ibrance), to evaluate their safety and effectiveness in treating certain types of breast cancer. It specifically targets postmenopausal women with HR-positive, HER2-negative metastatic breast cancer. The trial includes two groups: one uses the treatment as the first step, while the other applies it for ongoing care after initial chemotherapy. Eligible participants should have breast cancer that has spread beyond the original site and matches the specified hormone and protein profiles. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot use drugs that are strong CYP3A4 inhibitors or inducers. It's best to discuss your current medications with the study team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of anastrozole and palbociclib has been well tolerated in previous studies. In one study, this treatment, when used with other drugs, proved effective for 97% of patients. Most patients responded well and did not experience severe side effects. This combination is currently undergoing testing in a Phase 2 trial, indicating some evidence of safety from earlier studies, but more research is needed to confirm these findings. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Anastrozole combined with Palbociclib for breast cancer because they target the disease in a unique way. Unlike traditional treatments that often focus solely on hormone receptor pathways, this combination adds a cell cycle inhibitor, Palbociclib, which interrupts cancer cell division. This dual approach not only aims to halt tumor growth more effectively but also offers a promising first-line and maintenance therapy option, potentially improving outcomes for patients.

What evidence suggests that this trial's treatments could be effective for breast cancer?

Research has shown that using anastrozole and palbociclib together effectively treats HR-positive, HER2-negative metastatic breast cancer. In this trial, participants will receive this combination as either first-line or maintenance therapy. Studies indicate that this combination, particularly when palbociclib is paired with aromatase inhibitors like anastrozole, is effective for about 28.8 months in similar patients. Real-world data also supports its effectiveness, showing a 69.4% clinical benefit rate when used as the first treatment. This indicates that many patients experience positive results with this treatment. Overall, strong evidence supports the use of this combination for this type of breast cancer. ^{1 3 6 7 8}

Who Is on the Research Team?

Antoinette Tan, MD

Principal Investigator

Atrium Health (formerly Carolinas HealthCare System)

Are You a Good Fit for This Trial?

This trial is for postmenopausal women with HR-positive, HER2-negative metastatic breast cancer. It's open to those who haven't had treatment for metastatic disease (Cohort A) or as maintenance after first-line chemo (Cohort B). Participants need measurable disease, good performance status, and normal organ function. Pre/peri-menopausal women must be on LHRH agonist therapy.

Inclusion Criteria

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

My cancer can be measured by scans or is only in my bones.

I have not received treatment for metastatic disease in Cohort A.

Exclusion Criteria

I do not have active brain metastases or related conditions.

You are allergic to anastrozole.

I am not taking any strong medications that affect liver enzymes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anastrozole daily and palbociclib on Days 1-21 of a 28-day cycle

Approximately 4 years or until disease progression, unacceptable toxicity, participant withdrawal, or investigator decision

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Anastrozole
• Palbociclib

Trial Overview The study tests combining anastrozole with palbociclib in two groups: one receiving it as a first-line therapy and the other as maintenance post-chemo. It's an open-label pilot study where patients are assigned to either Cohort A or B based on their treatment history.

How Is the Trial Designed?

Group I: Cohort B: Maintenance therapy Experimental Treatment 2 Interventions

Anastrozole by mouth daily and palbociclib by mouth Days 1-21 on a 28 day cycle

Group II: Cohort A: First-line therapy Experimental Treatment 2 Interventions

Anastrozole by mouth daily and palbociclib by mouth Days 1-21 on a 28 day cycle

Anastrozole is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Arimidex for:

• Breast cancer
• Early breast cancer in postmenopausal women

Approved in United States as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• First-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer

Approved in Canada as Arimidex for:

• Adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer
• Treatment of postmenopausal women with hormone receptor-positive advanced breast cancer

Approved in Japan as Arimidex for:

• Breast cancer

Who Is Running the Clinical Trial?

Antoinette Tan, MD

Lead Sponsor

Trials

3

Recruited

80+

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Atrium Health Levine Cancer Institute

Collaborator

Trials

30

Recruited

4,700+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Published Research Related to This Trial

Anastrozole is a potent and selective third-line aromatase inhibitor that offers a significant advancement in the treatment of hormone-sensitive breast cancer, particularly for postmenopausal women.

This review highlights anastrozole's biochemical properties and clinical efficacy, indicating its widespread use as a first- and second-line treatment option, potentially providing better outcomes and safety compared to traditional therapies like tamoxifen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. Köberle, D., Thürlimann, B.[2018]

Anastrozole, a highly specific aromatase inhibitor, has emerged as a potentially better tolerated and more effective treatment for postmenopausal patients with hormone-sensitive breast cancer compared to tamoxifen, which has safety and tolerability issues.

The ongoing Arimidex, Tamoxifen, Alone or in Combination trial indicates that anastrozole is an effective and well-tolerated option for adjuvant endocrine treatment in early breast cancer, suggesting its potential role in chemoprevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of anastrozole in adjuvant therapy for postmenopausal patients. Buzdar, AU.[2019]

In a study of 6241 postmenopausal women with early-stage breast cancer, anastrozole was found to have significantly fewer treatment-related adverse events compared to tamoxifen, indicating better tolerability.

Anastrozole also demonstrated a more favorable risk-benefit profile, with lower rates of serious adverse events and recurrence compared to tamoxifen, making it a preferable option for adjuvant treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive side-effect profile of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: long-term safety analysis of the ATAC trial. Buzdar, A., Howell, A., Cuzick, J., et al.[2022]

In a retrospective analysis of the ATAC trial, women taking tamoxifen experienced significantly more gynecologic adverse events (34.2%) compared to those taking anastrozole (20.5%), leading to more medical interventions, including a nearly fourfold increase in hysterectomies.

The findings support the use of anastrozole as the preferred initial treatment for early hormone receptor-positive breast cancer due to its lower incidence of gynecologic complications, particularly since most adverse events with tamoxifen occurred within the first 2.5 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A lower incidence of gynecologic adverse events and interventions with anastrozole than with tamoxifen in the ATAC trial. Duffy, SR., Distler, W., Howell, A., et al.[2018]

Anastrozole is more effective than tamoxifen in improving disease-free survival and reducing tumor recurrence in postmenopausal women with hormone receptor-positive early breast cancer, as shown in the ATAC trial with significant relative risk reductions of 17% and 19%.

Anastrozole has a better safety profile compared to tamoxifen, with lower rates of side effects such as vaginal bleeding, hot flushes, and thromboembolic events, while both treatments had similar impacts on patient quality of life during the first two years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole: in early breast cancer. Wellington, K., Faulds, DM.[2018]

Oral palbociclib is an effective treatment for HR-positive, HER2-negative advanced or metastatic breast cancer, significantly prolonging progression-free survival when used with letrozole or fulvestrant in clinical trials involving postmenopausal women.

The most common side effect was neutropenia, which was manageable and rarely led to serious complications, indicating that palbociclib can be safely administered without significantly compromising its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palbociclib: A Review in HR-Positive, HER2-Negative, Advanced or Metastatic Breast Cancer. Kim, ES., Scott, LJ.[2022]

Palbociclib, an inhibitor of CDK4 and CDK6, was granted accelerated FDA approval for treating advanced breast cancer in postmenopausal women when combined with letrozole, based on a trial involving 165 patients that showed significant improvement in progression-free survival (PFS).

The trial demonstrated a nearly 50% reduction in the risk of disease progression for patients receiving the combination therapy compared to those on letrozole alone, although the most common side effect noted was neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer. Beaver, JA., Amiri-Kordestani, L., Charlab, R., et al.[2022]

Palbociclib is the first CDK4/6 inhibitor approved for treating estrogen receptor-positive, HER2-negative metastatic breast cancer, and it works by selectively inhibiting CDK4 and CDK6, enhancing the effects of anti-estrogens like letrozole and fulvestrant.

Clinical trials show that palbociclib significantly doubles the treatment efficacy of letrozole and fulvestrant while maintaining a manageable safety profile, positively impacting patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety and efficacy of palbociclib in the treatment of metastatic breast cancer. Ettl, J., Harbeck, N.[2017]

Anastrozole is as effective as tamoxifen for treating advanced breast cancer in postmenopausal women, showing a slightly higher objective response rate (21% vs. 17%) and a significant clinical benefit in 59% of patients compared to 46% for tamoxifen.

Anastrozole offers a significant advantage in time to progression (median of 11.1 months vs. 5.6 months for tamoxifen) and has a lower incidence of side effects, such as thromboembolic events and vaginal bleeding, making it a preferable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. Nabholtz, JM., Buzdar, A., Pollak, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9553912/

Real-world study of overall survival with palbociclib plus ... The 5-year survival rate for de novo MBC is only 29.0%. The majority (68%) of breast cancer cases have a hormone receptor–positive (HR+)/human ...

2. breast-cancer-research.biomedcentral.com breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-023-01678-5

Effectiveness of palbociclib with aromatase inhibitors for the ... Data suggest palbociclib with AI to have an effectiveness of 28.8 months, when used in patients with overlapping characteristics to those used in PALOMA-2.

3. onclive.com onclive.com/view/real-world-outcomes-support-use-of-first-line-palbociclib-plus-et-in-hr-her2-advanced-breast-cancer

Real-World Outcomes Support Use of First-Line Palbociclib ... Real-world data supported the clinical effectiveness of first-line palbociclib plus endocrine therapy in HR-positive, HER2-negative breast ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0960977625004655

metastatic breast cancer: A Flatiron Health database analysis However, a few studies have found palbociclib dose reductions to be associated with longer rwPFS or overall survival (OS), but in some instances the impact was ...

5. academic.oup.com academic.oup.com/oncolo/article/30/7/oyae291/7852806

Real-world effectiveness of palbociclib plus endocrine therapy ... Real-world response and clinical benefit rates with palbociclib + ET were 34.0% and 69.4%, respectively, in 1L, and 21.8% and 57.9% in ≥2L.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.00137

Overall Survival With Palbociclib Plus Letrozole in ... The median OS was 53.9 months (95% CI, 49.8 to 60.8) with palbociclib plus letrozole versus 51.2 months (95% CI, 43.7 to 58.9) with placebo plus ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04711252

NCT04711252 | A Comparative Study of AZD9833 Plus ... The goal of the study is to demonstrate superiority of AZD9833 over anastrozole in the context of combination with palbociclib in first line setting.

8. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/RF02-01/744290/Abstract-RF02-01-A-Multicenter-Phase-I-II-Trial-of

Abstract RF02-01: A Multicenter, Phase I/II Trial of Anastrozole ... The combination of anastrozole, palbociclib, trastuzumab, and pertuzumab was well tolerated and effective with a clinical benefit rate of 97% in pts with ...