Hormone Therapy + Chemotherapy for Breast Cancer

(TAILORx Trial)

Recruiting at 1330 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must be taking: Hormone therapy

Must not be taking: SERMs, Aromatase inhibitors

Disqualifiers: Chronic obstructive pulmonary disease, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 3

Duration: 5-10 years

10273 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies the best individual therapy for women who have node-negative, estrogen-receptor positive breast cancer by using a special test (Oncotype DX), and whether hormone therapy alone or hormone therapy together with combination chemotherapy is better for women who have an Oncotype DX recurrence score of 11-25. Estrogen can cause the growth of breast cancer cells. Hormone therapy may fight breast cancer by blocking the use of estrogen by the tumor cells or by lowering the amount of estrogen the body makes. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving hormone therapy together with more than one chemotherapy drug (combination chemotherapy) has been shown to reduce the chance of breast cancer recurrence, but the benefit of adding chemotherapy to hormone therapy for women with node-negative, estrogen-receptor positive breast cancer is small. New tests may provide information about which patients are more likely to benefit from chemotherapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are taking certain hormone therapies like selective estrogen-receptor modulators or aromatase inhibitors, you may need to stop if they were for breast cancer prevention or other indications.

What data supports the effectiveness of the drug combination of hormone therapy and chemotherapy for breast cancer?

Research shows that drugs like anastrozole and letrozole, which are part of the hormone therapy, are effective in treating breast cancer in postmenopausal women, especially when other treatments like tamoxifen have not worked. These drugs have been found to improve disease-free survival and have a better safety profile compared to older treatments. ^{1 2 3 4 5}

Is hormone therapy with anastrozole safe for breast cancer treatment?

Research shows that anastrozole, used in hormone therapy for breast cancer, generally has a favorable safety profile compared to tamoxifen. It is considered well-tolerated and potentially less toxic than some other treatments. ^{1 2 6 7 8}

How is the drug combination of Anastrozole, Exemestane, Letrozole, and Tamoxifen Citrate unique for breast cancer treatment?

This drug combination is unique because it includes both aromatase inhibitors (Anastrozole, Exemestane, Letrozole) and Tamoxifen, which work together to block estrogen production and action, offering a comprehensive approach to treating hormone receptor-positive breast cancer in postmenopausal women. This combination is considered more effective and better tolerated than older treatments like megestrol acetate. ^{1 5 9 10 11}

Research Team

Joseph A Sparano

Principal Investigator

ECOG-ACRIN Cancer Research Group

Eligibility Criteria

This trial is for women with node-negative, estrogen-receptor positive breast cancer who have had surgery. They should expect to live at least 10 years and not have received prior radiation or chemotherapy for this cancer. Participants must not be pregnant, breastfeeding, or have serious health issues like heart failure or chronic liver disease.

Inclusion Criteria

Negative axillary nodes

I have had surgery for breast cancer.

My cancer is positive for estrogen and/or progesterone receptors.

Exclusion Criteria

I am receiving treatment for chronic obstructive pulmonary disease.

I have had a stroke before.

Chronic psychiatric condition or other condition impairing compliance with treatment regimen

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive hormonal therapy alone or combination chemotherapy and hormonal therapy based on Oncotype DX recurrence score

5-10 years

Regular visits as per treatment protocol

Radiotherapy

Patients who have had breast-conservation surgery receive radiotherapy

4-8 weeks

Radiotherapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

20 years

Every 3-6 months for 5 years, then annually

Treatment Details

Interventions

• Anastrozole
• Combination Chemotherapy
• Exemestane
• Letrozole
• Tamoxifen Citrate

Trial Overview The study tests if hormone therapy alone or combined with chemotherapy is more effective in women with certain Oncotype DX recurrence scores. It examines the role of estrogen in tumor cell growth and whether blocking it or reducing its production can better prevent cancer recurrence.

Participant Groups

Group I: Group 3 (Oncotype DX recurrence score >= 26) Experimental Treatment 7 Interventions

Patients in this group receive combination chemotherapy followed by hormone therapy similar to the patients in group two who are assigned to receive both types of treatment.

Group II: Group 2, Arm I (experimental) Experimental Treatment 6 Interventions

Patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.

Group III: Group 1 (Oncotype DX recurrence score =< 10) Experimental Treatment 7 Interventions

Patients in this group receive hormone therapy with tamoxifen, anastrozole, letrozole, or exemestane PO for up to 5 years. Some patients then continue to receive hormone therapy for an additional 5 years.

Group IV: Group 2, Arm II (standard) Active Control 7 Interventions

Patients receive standard combination chemotherapy at the discretion of the treating physician. Within 4 weeks after the last dose of chemotherapy, patients receive hormonal therapy as in Group 1 at the discretion of the treating physician.

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Cancer and Leukemia Group B

Collaborator

Trials

81

Recruited

118,000+

SWOG Cancer Research Network

Collaborator

Trials

403

Recruited

267,000+

Southwest Oncology Group

Collaborator

Trials

389

Recruited

260,000+

NSABP Foundation Inc

Collaborator

Trials

89

Recruited

140,000+

American College of Surgeons

Collaborator

Trials

18

Recruited

60,400+

North Central Cancer Treatment Group

Collaborator

Trials

49

Recruited

81,100+

NCIC Clinical Trials Group

Collaborator

Trials

190

Recruited

145,000+

Findings from Research

Anastrozole and letrozole are effective oral treatments for advanced breast cancer in postmenopausal women, especially when other therapies like tamoxifen have not worked.

Both drugs are claimed to be more effective and less toxic than the standard treatment, megestrol acetate, although the review assesses the validity of these claims.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

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]

In a study of 150 breast cancer patients, those receiving sequential treatment with letrozole and tamoxifen showed a higher overall response rate and fewer adverse reactions compared to those on letrozole alone.

Both treatment methods resulted in similar survival rates, but the sequential therapy group had a significantly lower recurrence rate and better improvement in blood lipid levels, indicating a potentially better prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma. Lu, X., Qian, C.[2023]

In a study involving 6182 postmenopausal women with hormone-receptor-positive breast cancer, sequential treatment with tamoxifen and letrozole did not significantly improve disease-free survival compared to letrozole monotherapy, indicating that letrozole alone may be sufficient for treatment.

The updated analysis showed no statistically significant difference in overall survival between letrozole and tamoxifen monotherapy, suggesting that both treatments have similar long-term outcomes, with adverse events consistent with previous reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. Mouridsen, H., Giobbie-Hurder, A., Goldhirsch, A., et al.[2022]

Adjuvant hormonal therapy with tamoxifen significantly reduces the risk of breast cancer recurrence and death in women with early-stage, hormone receptor-positive breast cancer, but it also carries risks of endometrial cancer and thromboembolic events.

Recent trials, including the MA-17 and Intergroup Exemestane Study, show that selective aromatase inhibitors (AIs) like anastrozole and exemestane provide superior disease-free survival compared to tamoxifen, establishing AIs as a preferred treatment option for postmenopausal women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know? Chung, CT., Carlson, RW.[2019]

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]

The ATAC trial, involving over 9,000 postmenopausal women, demonstrated that anastrozole significantly improves disease-free survival and reduces recurrence rates compared to tamoxifen, with benefits continuing even after treatment ends.

Anastrozole also has a favorable safety profile compared to tamoxifen, suggesting it may be a better initial treatment option for early breast cancer, especially when considering long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. Buzdar, AU., Cuzick, J.[2018]

The ATAC trial is one of the few studies that directly compares aromatase inhibitors (AIs) for breast cancer treatment, providing valuable insights into their effectiveness.

Emerging evidence suggests a proposed sequence of hormonal therapies, including anastrozole and tamoxifen, tailored for different patient populations, which could optimize treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hormonal therapy in early and advanced breast cancer. Buzdar, AU.[2019]

Aromatase inhibitors like anastrozole, letrozole, and exemestane are now the preferred hormonal treatments for estrogen-receptor-positive, postmenopausal metastatic breast cancer, replacing older therapies such as tamoxifen.

Recent studies have confirmed the effectiveness of these aromatase inhibitors in managing breast cancer, highlighting their critical role in targeting the hormonal pathways involved in the disease's progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonsteroidal and steroidal aromatase inhibitors in breast cancer. Hamilton, A., Volm, M.[2018]

Third-generation aromatase inhibitors (AIs) like anastrozole, letrozole, and exemestane have emerged as effective alternatives to tamoxifen for treating postmenopausal breast cancer, particularly in hormone receptor-positive cases, as shown in the ATAC trial with over five years of follow-up.

Fulvestrant, a new type of estrogen receptor antagonist with no partial agonist activity, represents a promising option in breast cancer treatment, and the review discusses future sequencing strategies for using AIs earlier in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New developments in the treatment of postmenopausal breast cancer. Howell, A.[2018]

References

1. England pubmed.ncbi.nlm.nih.gov

New aromatase inhibitors for breast cancer. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Anastrozole: pharmacological and clinical profile in postmenopausal women with breast cancer. [2018]

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

Efficacy, Safety, and Prognosis of Sequential Therapy with Tamoxifen and Letrozole versus Letrozole Monotherapy for Breast Carcinoma. [2023]

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

Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. [2022]

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

Adjuvant aromatase inhibitors following tamoxifen for early-stage breast cancer in postmenopausal women: what do we really know? [2019]

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

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

7. England 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. [2022]

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

Anastrozole as an adjuvant endocrine treatment for postmenopausal patients with breast cancer: emerging data. [2018]

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

Hormonal therapy in early and advanced breast cancer. [2019]

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

Nonsteroidal and steroidal aromatase inhibitors in breast cancer. [2018]

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

New developments in the treatment of postmenopausal breast cancer. [2018]