Hormone Therapy + Chemotherapy for Breast Cancer

(TAILORx Trial)

Not currently recruiting at 1369 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether hormone therapy alone or combined with chemotherapy is more effective for certain breast cancers. It targets women with node-negative, estrogen-receptor positive breast cancer, using a special test to identify those who might benefit from added chemotherapy. Hormone therapy, including drugs like Anastrozole, Exemestane, Letrozole, and Tamoxifen Citrate, blocks or lowers estrogen to slow or stop cancer growth. Chemotherapy aims to kill cancer cells or prevent their spread. Women who have had breast cancer surgery and meet specific medical criteria may qualify for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Previous studies have shown that anastrozole greatly lowers the risk of breast cancer recurrence and reduces the chance of death from it. It also provides long-term protection for women at high risk. Exemestane is considered safer and more effective than tamoxifen, another common treatment, significantly lowering the risk of breast cancer in at-risk women. Letrozole has also proven effective in preventing new cases of breast cancer and improving survival rates.

Tamoxifen reduces the risk of breast cancer and decreases the chance of dying from it. It has been effective for many years. In combination with other chemotherapy treatments, about 20-30% of patients report severe side effects. However, it still improves outcomes when used with other treatments.

These treatments are generally well-tolerated, but awareness of possible side effects is important. Depending on the trial phase, strong evidence supports the safety of these treatments in humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial because they explore combining hormone therapy and chemotherapy, which could offer a more personalized approach to breast cancer care. Unlike standard treatments that typically use either hormone therapy or chemotherapy based on certain criteria, this study investigates using both together in specific ways based on a patient's Oncotype DX recurrence score. This approach aims to tailor treatment more precisely to the individual's cancer profile, potentially improving outcomes by targeting cancer more effectively with a combination of therapies. Additionally, using hormone therapy for extended periods shows promise in providing long-term benefits and reducing the risk of recurrence.

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

Research has shown that hormone treatments like anastrozole, exemestane, letrozole, and tamoxifen citrate effectively treat estrogen-receptor positive breast cancer. In this trial, participants in Group 1 will receive hormone therapy with one of these medications. Anastrozole can lower the chance of cancer recurrence by 41% and reduce the risk of dying from breast cancer by 34%. Exemestane can decrease the risk of cancer returning or causing death by 24% compared to tamoxifen. Letrozole also helps prevent cancer recurrence and extends the time patients remain cancer-free. Tamoxifen has been shown to cut the risk of dying from breast cancer by one-third over 15 years.

Participants in Group 3 will receive combination chemotherapy followed by hormone therapy, similar to those in Group 2, Arm II, who receive both treatments. Adding combination chemotherapy to hormone therapy can further reduce the chance of breast cancer returning, although the benefit might be small for early-stage cancer that hasn't spread to the lymph nodes. ^{1 2 3 6 7}

Who Is on the Research Team?

Joseph A Sparano

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

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

Chronic psychiatric condition or other condition impairing compliance with treatment regimen

I am receiving treatment for chronic obstructive pulmonary disease.

I have had a stroke before.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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]

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 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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2690973/

Long-term efficacy and safety of anastrozole for adjuvant ... The results of the Oxford meta-analyses3,4 have demonstrated significant reduction in both disease recurrence (41%) and breast cancer specific mortality (34%) ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(19)32955-1/fulltext

Use of anastrozole for breast cancer prevention (IBIS-II) Two large clinical trials have shown a reduced rate of breast cancer development in high-risk women in the initial 5 years of follow-up after use of aromatase ...

3. breastcancer.org breastcancer.org/research-news/10-years-arimidex

10 Years of Arimidex Reduces Recurrence Risk ... Taking Arimidex for 10 years after breast cancer surgery reduced recurrence risk, but didn't improve overall survival.

4. news.cancerresearchuk.org news.cancerresearchuk.org/2023/11/07/anastrozole-licensed-prevent-breast-cancer-high-risk-women/

Thousands of women offered anastrozole to help prevent ... Cases of invasive oestrogen receptor-positive breast cancer specifically were reduced by 54%, and ductal carcinoma in situ by 59%, especially in ...

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.00994

Final Overall Survival in the Phase III FALCON Trial The randomized phase III FALCON trial demonstrated significant improvement in progression-free survival (PFS) with fulvestrant versus anastrozole in ...

6. ahajournals.org ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.044750

Aromatase Inhibitors and the Risk of Cardiovascular ... These drugs have been associated with favorable clinical outcomes, including decreased risks of all-cause and breast cancer–related mortality, ...

7. breastcancer.org breastcancer.org/research-news/risk-reducing-effects-of-arimidex-last-years

Risk-Reducing Effects of Arimidex for High- ... The new results show that women who took Arimidex were 50% less likely to be diagnosed with breast cancer than women who didn't take Arimidex.