Hormone + HER2-targeted Therapy for Breast Cancer

(ADEPT Trial)

Recruiting at 27 trial locations

Overseen By Adrienne Waks, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must be taking: Hormonal therapy

Must not be taking: Investigational agents

Disqualifiers: Pregnancy, Nursing, Advanced tumors, 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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 18

Duration: 1 year for HER2-directed treatment, 5 years for hormonal therapy

375 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you must stop any hormonal contraceptive therapy before joining the study.

What data supports the effectiveness of the drug combination of hormone therapy and HER2-targeted therapy for breast cancer?

Research shows that hormone therapy is effective for hormone receptor-positive breast cancer, improving survival and quality of life. HER2-targeted therapies, like Trastuzumab and Pertuzumab, are effective in treating HER2-positive breast cancer, often used alongside hormone therapy to manage resistance and improve outcomes. ^{1 2 3 4 5}

Is hormone and HER2-targeted therapy for breast cancer generally safe for humans?

Hormone therapies, like endocrine therapy, are generally considered safe with manageable side effects, but targeted therapies for breast cancer can have complex and potentially severe side effects that require careful management. ^{1 3 5 6 7}

How is the Hormone + HER2-targeted Therapy treatment different for breast cancer?

This treatment is unique because it combines hormone therapy with HER2-targeted therapy, addressing both hormone receptor-positive and HER2-positive breast cancer. This dual approach aims to overcome resistance that can occur when these therapies are used separately, potentially improving outcomes for patients with this specific type of breast cancer. ^{3 4 6 8 9}

What is the purpose of this trial?

This research study is studying a combination of HER2-directed therapies (trastuzumab and pertuzumab) and hormonal therapy as a treatment after surgery for hormone receptor positive breast cancer. The study drugs involved in this study are: * A combination of trastuzumab and pertuzumab given as an injection under the skin (PHESGO) * Hormonal (endocrine) Treatment

Research Team

Adrienne Waks, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

This trial is for adults with early-stage hormone receptor-positive, HER2-positive breast cancer who've had surgery. It's open to those who may have received short-term pre-surgery treatment or up to 8 weeks of hormonal therapy post-surgery. Participants must be willing to stop contraceptive hormones and provide tissue samples. Excluded are pregnant/nursing women, those with severe illnesses, previous invasive breast cancers, or anyone on other investigational drugs.

Inclusion Criteria

I have had surgery for my current breast cancer.

I have a small, ER+ (≥ 10%), HER2-negative tumor in addition to my primary HER2 positive tumor.

Both of my breasts have cancers that qualify for the trial.

Exclusion Criteria

I am not pregnant, nursing, or if capable of becoming pregnant, I am willing to use contraception.

I have had breast cancer before.

I am a man not willing to use birth control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HER2-directed treatment for 1 year and hormonal therapy for approximately 5 years

1 year for HER2-directed treatment, 5 years for hormonal therapy

18 cycles of 21-day intervals for HER2-directed treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 years

Treatment Details

Interventions

• ADJUVANT ENDOCRINE THERAPY
• Pertuzumab
• Trastuzumab

Trial Overview The study tests a combination of trastuzumab and pertuzumab (PHESGO) injections plus hormonal therapy as post-surgical treatment for specific breast cancer patients. The goal is to evaluate the effectiveness of this combined HER2-directed and endocrine therapy in preventing cancer recurrence.

Participant Groups

Group I: PERTUZUMAB + TRASTUZUMAB + ADJUVANT ENDOCRINE THERAPY Experimental Treatment 2 Interventions

Study treatment will be administered in 21-day (3- week, +/- 3 days) cycles for one year (18 cycles). * Trastuzumab + Pertuzumab SC fixed dose combination * Hormonal therapy- oral, daily per cycle (may add LHRH agonist per investigator discretion)

ADJUVANT ENDOCRINE THERAPY is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Hormone therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer

Approved in United States as Endocrine therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer
• Ovarian cancer

Approved in Canada as Hormone therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer

Approved in Japan as Endocrine therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer

Approved in China as Hormone therapy for:

• Breast cancer
• Prostate cancer

Approved in Switzerland as Endocrine therapy for:

• Breast cancer
• Prostate cancer
• Endometrial cancer

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

Findings from Research

For low-risk ER+ HER2- breast cancer patients, five years of endocrine therapy (ET) is standard, with Tamoxifen recommended for premenopausal women and aromatase inhibitors (AIs) for postmenopausal women, demonstrating effective management with manageable side effects.

In high-risk patients, combining ET with ovarian function suppression (OFS) and two years of Abemaciclib is advised, while extended ET beyond five years may be beneficial, although the optimal duration for AIs remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Appraising Adjuvant Endocrine Therapy in Hormone Receptor Positive HER2-Negative Breast Cancer-A Literature Review. Mata, DGMM., Amir Carmona, C., Eisen, A., et al.[2022]

Endocrine therapy is the first-line treatment for women with hormone receptor-positive metastatic breast cancer due to its effectiveness and lower toxicity compared to chemotherapy, aiming to maintain quality of life and prolong survival.

Various classes of endocrine therapies, including aromatase inhibitors and selective estrogen modulators, are available, but resistance to these treatments eventually develops, highlighting the need for optimal timing and sequencing of therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extending the clinical benefit of endocrine therapy for women with hormone receptor-positive metastatic breast cancer: differentiating mechanisms of action. Glück, S.[2014]

Aromatase inhibitors (AIs) are more effective than tamoxifen for treating estrogen receptor-positive (ER+)/HER2+ breast cancer, particularly in the adjuvant setting.

Combining HER2-targeted therapy, like trastuzumab, with AIs significantly improves progression-free survival and response rates in postmenopausal women, suggesting a beneficial interaction between HER2 and estrogen receptor signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of biologic therapy and chemotherapy in hormone receptor- and HER2-positive breast cancer. Buzdar, AU.[2020]

Endocrine therapies are the primary treatment for hormone-dependent breast cancer, but many patients face tumor relapse due to acquired resistance, particularly in cases where the tumor overexpresses HER2, which is found in about 10% of all breast cancer cases.

The review highlights the need for new therapeutic strategies to overcome resistance to endocrine therapies, especially in ER+/HER2+ tumors, as current treatments often involve a combination of HER2-targeted therapies and endocrine treatments, which may have different interactions and efficacy profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human epidermal growth factor receptor-2 and endocrine resistance in hormone-dependent breast cancer. Alataki, A., Dowsett, M.[2022]

Adjuvant endocrine therapy is crucial for treating hormone-receptor positive, HER2 negative breast cancers, especially in postmenopausal women, as it significantly reduces the risk of recurrence and improves overall survival.

Recent advancements include the use of aromatase inhibitors and extended treatment durations beyond the traditional 5 years, highlighting the importance of tailoring therapy based on tumor characteristics and managing treatment-related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant endocrine therapy in postmenopausal women: making treatment choices based on the magnitude of benefit. Burstein, HJ.[2020]

In a systematic review of six randomized controlled trials involving 5390 patients, both tamoxifen and aromatase inhibitors showed similar disease-free survival rates as adjuvant endocrine therapies for HER2-positive, hormone receptor-positive early breast cancer.

The analysis indicated no significant difference in effectiveness between the two treatments, suggesting that either option could be viable for patients, but further large-scale studies are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant endocrine therapy in HER2-positive breast cancer patients: systematic review and meta-analysis. Peleg Hasson, S., Brezis, MR., Shachar, E., et al.[2021]

Targeted agents like CDK4/6 inhibitors have improved outcomes for patients with HR-positive, HER2-negative metastatic breast cancer compared to traditional endocrine therapies, but they come with complex and potentially severe adverse events that require careful management.

Despite the increased risk of hematologic toxicities and the need for more frequent physician visits, these side effects are generally manageable without needing to consult specialists, highlighting the importance of a multidisciplinary approach in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success. Cazzaniga, ME., Danesi, R., Girmenia, C., et al.[2020]

In a study of 147 HER2+ metastatic breast cancer patients, those who received concurrent endocrine therapy (ET) alongside first-line dual anti-HER2 therapy showed significantly improved 5-year progression-free survival (PFS) and overall survival (OS) compared to those who did not receive ET.

The addition of ET did not lead to an increase in adverse events, suggesting that it is a safe and effective option for enhancing treatment outcomes in HER2+/HR+ patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer. Loft, M., Lok, SW., De Boer, R., et al.[2023]

For postmenopausal women with estrogen receptor-positive metastatic breast cancer, combining endocrine therapy with anti-HER2 therapy may offer a new treatment strategy, especially for those with good performance status and low tumor burden.

This approach could potentially delay the need for chemotherapy, which is often more toxic, by addressing the resistance that HER2 overexpression may cause against endocrine therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A shift in the treatment of hormone receptor and human epidermal growth factor receptor 2-positive metastatic breast cancer. Kemp, Z., Jones, A.[2014]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Appraising Adjuvant Endocrine Therapy in Hormone Receptor Positive HER2-Negative Breast Cancer-A Literature Review. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Extending the clinical benefit of endocrine therapy for women with hormone receptor-positive metastatic breast cancer: differentiating mechanisms of action. [2014]

3. England pubmed.ncbi.nlm.nih.gov

Role of biologic therapy and chemotherapy in hormone receptor- and HER2-positive breast cancer. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Human epidermal growth factor receptor-2 and endocrine resistance in hormone-dependent breast cancer. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Adjuvant endocrine therapy in postmenopausal women: making treatment choices based on the magnitude of benefit. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Adjuvant endocrine therapy in HER2-positive breast cancer patients: systematic review and meta-analysis. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Management of toxicities associated with targeted therapies for HR-positive metastatic breast cancer: a multidisciplinary approach is the key to success. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Addition of endocrine therapy to dual anti-HER2 targeted therapy in initial treatment of HER2 + /HR + metastatic breast cancer. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

A shift in the treatment of hormone receptor and human epidermal growth factor receptor 2-positive metastatic breast cancer. [2014]