Chemotherapy Reduction After Surgery for Breast Cancer

Not currently recruiting at 1067 trial locations

Overseen By Leon C. Hwang

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: ECOG-ACRIN Cancer Research Group

Must be taking: HER2-targeted therapy

Disqualifiers: Stage IV cancer, T4/N3 disease, 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: 18

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether some patients with HER2-positive breast cancer can skip further chemotherapy after surgery. It targets those with no remaining cancer in the breast or lymph nodes following initial treatment. The study evaluates the effectiveness of paclitaxel (a chemotherapy drug), along with trastuzumab and pertuzumab (both targeted therapies), in preventing cancer recurrence without additional chemotherapy. It may suit individuals diagnosed with HER2-positive stage II-IIIa breast cancer who have undergone surgery with no residual cancer. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that patients must be willing to receive standard adjuvant therapy, which may include certain medications. It's best to discuss your current medications with the trial team to get a clear answer.

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

Previous studies showed that when pertuzumab was combined with trastuzumab and chemotherapy, common side effects included diarrhea, hair loss, and low blood counts. More serious reactions, such as allergies, occurred in about 11% of patients. Trastuzumab often led to fever, nausea, and vomiting. Most people managed these side effects well, though some required changes in their treatment. Paclitaxel, another widely used drug, is generally well-tolerated but can also cause hair loss and low blood counts. These treatments have already been approved for certain types of breast cancer, indicating their safety is well-known. However, ongoing studies continue to gather more information about using them in new ways or combinations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for breast cancer because they aim to reduce the need for chemotherapy after surgery, which can lessen the side effects patients experience. Unlike standard treatments that might require extensive chemotherapy post-surgery, this approach tailors therapy based on patient response. For patients who achieve a complete response (pCR) after surgery, the focus shifts to targeted therapies like trastuzumab and pertuzumab, which work by targeting specific proteins on cancer cells. Meanwhile, those with residual disease receive trastuzumab emtansine, combining targeted therapy with a chemotherapy agent, potentially offering a more effective and personalized treatment. This strategic, response-based approach could lead to more effective and less toxic treatment plans.

What evidence suggests that this trial's treatments could be effective for HER2-positive breast cancer?

In this trial, participants will receive different treatments based on their response to surgery. Research has shown that paclitaxel, trastuzumab, and pertuzumab can effectively treat HER2-positive breast cancer. Paclitaxel stops cancer cells from growing and spreading. Studies have found that nab-paclitaxel, a type of paclitaxel, can delay breast cancer progression. Trastuzumab and pertuzumab target HER2 receptors on cancer cells, blocking signals that promote growth and aiding the immune system in destroying them. These treatments have effectively shrunk tumors and improved outcomes for patients with HER2-positive breast cancer. Participants in Arm A, who achieve a pathological complete response (pCR) after surgery, will receive trastuzumab and pertuzumab. Meanwhile, participants in Arm B, with residual invasive disease after surgery, will receive trastuzumab emtansine. ^{6 7 8 9 10}

Who Is on the Research Team?

Nadine M Tung

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for HER2-positive stage II-IIIa breast cancer patients who've had pre-surgery chemo and targeted therapy with no remaining cancer. They must have proper organ function, no history of invasive breast cancer except certain conditions, not be pregnant or breastfeeding, willing to use contraception, and free from serious medical conditions that could affect study participation.

Inclusion Criteria

My hepatitis B virus is undetectable with treatment.

My cancer was stage II or IIIa when first diagnosed.

My cancer has not spread to my lymph nodes and the tumor is larger than 2.0 cm.

Exclusion Criteria

I've had the required scans for stage III disease or if I had abnormal liver tests or symptoms.

I do not have severe numbness or pain in my hands or feet.

I am currently on hormone therapy for a previous non-invasive breast cancer.

Timeline for a Trial Participant

Pre-operative/Neoadjuvant Therapy

Patients receive paclitaxel or nab-paclitaxel, trastuzumab, and pertuzumab intravenously. Treatment repeats every 21 days for up to 4 cycles.

12 weeks

4 cycles (in-person visits every 21 days)

Surgery

Patients undergo standard of care lumpectomy and/or mastectomy within 42 days after last dose of neoadjuvant therapy.

6 weeks

1 visit (in-person)

Post-operative/Adjuvant Therapy

Patients with pCR receive trastuzumab and pertuzumab every 21 days for up to 13 cycles. Patients with residual disease receive trastuzumab emtansine for 14 doses.

9 months

13 cycles (in-person visits every 21 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months for 2 years, every 6 months for 2-5 years, then annually for 5-15 years.

Long-term

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• Paclitaxel
• Pertuzumab
• Trastuzumab

Trial Overview

The trial tests if paclitaxel combined with trastuzumab and pertuzumab can eliminate the need for further chemotherapy after surgery in patients without remaining cancer post-pre-op treatment. These drugs aim to stop tumor growth by killing cells or blocking growth signals.

How Is the Trial Designed?

Group I: Arm B (residual invasive disease after surgery) Experimental Treatment 8 Interventions

PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel IV on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy. POST-OPERATIVE/ADJUVANT THERAPY: Patients with remaining tumor after surgery receive standard of care trastuzumab emtansine for 14 doses in the absence of disease progression or unacceptable toxicity. Patients may also receive additional standard of care chemotherapy, as well as hormone therapy if appropriate.

Group II: Arm A (pCR after surgery) Experimental Treatment 8 Interventions

PRE-OPERATIVE/NEOADJUVANT THERAPY: Patients receive either paclitaxel or nab-paclitaxel IV on days 1, 8 and 15, or docetaxel IV on day 1 at the discretion of the treating oncologist. Patients also receive trastuzumab IV on day 1 or days 1, 8, and 15, and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Within 42 days after last dose of neoadjuvant therapy, patients undergo standard of care lumpectomy and/or mastectomy. POST-OPERATIVE.ADJUVANT THERAPY: Patients with pCR after surgery receive trastuzumab and pertuzumab IV on day 1. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients may also undergo standard of care radiation therapy and receive hormone therapy if appropriate.

Who Is Running the Clinical Trial?

ECOG-ACRIN Cancer Research Group

Lead Sponsor

Trials

122

Recruited

160,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 57 patients with HER2-positive breast cancer receiving neoadjuvant treatment with doxorubicin and cyclophosphamide followed by trastuzumab and pertuzumab, only 3.5% developed severe heart failure, indicating a relatively low cardiac event rate.

The study found no increased risk of cardiotoxicity from the combination of trastuzumab and pertuzumab after doxorubicin-based chemotherapy, suggesting that this treatment regimen is cardiac safe for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Safety of Dual Anti-HER2 Therapy in the Neoadjuvant Setting for Treatment of HER2-Positive Breast Cancer. Yu, AF., Singh, JC., Wang, R., et al.[2018]

In a study of 30 patients with early-stage HER2+ breast cancer, the combination of trastuzumab and vinorelbine (TV) showed a high 5-year invasive disease-free survival rate of 90.9% and a perfect overall survival rate of 100% after a median follow-up of 68 months.

TV was well tolerated, with no cases of alopecia or long-term neuropathy reported, making it a promising alternative for patients who wish to avoid the side effects associated with traditional taxane-based regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvant trastuzumab and vinorelbine for early-stage HER2+ breast cancer. McLaughlin, S., Nakajima, E., Bar, Y., et al.[2023]

In a study of 152 patients with HER2-positive metastatic breast cancer, the combination of taxanes with trastuzumab and pertuzumab showed a significant progression-free survival (PFS) advantage over vinorelbine in patients with newly diagnosed metastatic disease, indicating a potential benefit for this specific group.

Overall, there was no significant difference in overall survival (OS) between the two treatment groups, suggesting that both taxanes and vinorelbine are viable options when combined with trastuzumab and pertuzumab for first-line treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Taxane versus vinorelbine in combination with trastuzumab and pertuzumab for first-line treatment of metastatic HER2-positive breast cancer: a retrospective two-center study. Reinhorn, D., Kuchuk, I., Shochat, T., et al.[2021]

Paclitaxel, when combined with doxorubicin, has shown a remarkable 95% objective response rate in chemotherapy-naive patients with metastatic breast cancer, indicating its high efficacy in treating this condition.

The treatment regimen demonstrated no signs of cardiac toxicity, allowing for further testing in patients with smaller tumors to potentially increase the rate of complete remission before surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Future developments for paclitaxel in the treatment of breast cancer. Bonadonna, G.[2015]

In the TRAIN-2 study involving 110 patients with HER2-positive breast cancer, the addition of pertuzumab to chemotherapy regimens resulted in neutropenia as the most common hematologic toxicity, affecting 53% of patients in the FEC-T arm and 51% in the PTC arm.

While both regimens showed manageable toxicity, the FEC-T arm had a higher incidence of asymptomatic ejection fraction decrease (24%) compared to the PTC arm (11%), and diarrhea was more common in the PTC arm (18% vs. 5%), indicating different toxicity profiles depending on the chemotherapy backbone used.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity of dual HER2-blockade with pertuzumab added to anthracycline versus non-anthracycline containing chemotherapy as neoadjuvant treatment in HER2-positive breast cancer: The TRAIN-2 study. van Ramshorst, MS., van Werkhoven, E., Honkoop, AH., et al.[2022]

In a study involving 397 patients with HER2-positive early breast cancer, treatment with pertuzumab and trastuzumab alongside anthracycline-containing regimens showed a low incidence of serious cardiac events, with only 1.5% experiencing class III/IV heart failure and 6.5% having declines in left ventricular ejection fraction in one treatment cohort.

The pathologic complete response (pCR) rates were high, at 61.8% and 60.7% for the two treatment cohorts, indicating that this combination therapy is both effective and maintains a favorable safety profile, consistent with previous studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study. Swain, SM., Ewer, MS., Viale, G., et al.[2022]

A study involving 808 patients with HER-2 positive breast cancer showed that adding pertuzumab to trastuzumab and docetaxel significantly improved overall survival, with a 3-year survival rate increase of 10% to 15%.

While pertuzumab did not worsen cardiac toxicity in patients with low cardiovascular risk, it was associated with increased side effects such as severe diarrhea and skin disorders, indicating the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab. Promising for some women with metastatic breast cancer, but more assessment needed. [2016]

In a study of 55 patients with early-stage, HER2-positive breast cancer, the neoadjuvant chemotherapy regimen combining epirubicin, cyclophosphamide, docetaxel, trastuzumab, and pertuzumab resulted in a high complete pathologic response rate of 64.8%.

The regimen demonstrated good cardiac safety, with only one case of significant left ventricular ejection fraction (LVEF) decline and no instances of symptomatic heart dysfunction, indicating that the treatment can be administered without major cardiac risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac safety of neoadjuvant chemotherapy with epirubicin and cyclophosphamide followed by docetaxel/pertuzumab/trastuzumab for HER2-positive breast cancer patients. Douganiotis, G., Grigoriadis, S., Kontovinis, L., et al.[2021]

The ASTER study demonstrated that a 6-month perioperative chemotherapy regimen combining Doxorubicin and Paclitaxel followed by Cyclophosphamide, Methotrexate, and 5-Fluorouracil is safe and effective for breast cancer treatment, with a low incidence of severe toxicities (8.5% grade III-IV hematologic toxicity).

With a follow-up of 6.7 years, the study reported high disease-free survival rates (99.6% at 1 year, 97.1% at 5 years) and overall survival rates (99.6% at 1 year, 94.9% at 5 years), indicating that this chemotherapy regimen is comparable in efficacy to other standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single Institution trial of anthracycline- and taxane-based chemotherapy for operable breast cancer: The ASTER study. Mariani, G., Galli, G., Cavalieri, S., et al.[2019]

In a study of 210 patients with ERBB2-positive metastatic breast cancer, the combination of trastuzumab and pertuzumab without chemotherapy showed a 24-month overall survival rate of 79.0%, which is comparable to 78.1% for those receiving the combination with chemotherapy.

Patients receiving the chemotherapy-free regimen had a median progression-free survival of 8.4 months, significantly shorter than the 23.3 months for those who received chemotherapy, but the absence of chemotherapy resulted in fewer adverse events and slight improvements in quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pertuzumab Plus Trastuzumab With or Without Chemotherapy Followed by Emtansine in ERBB2-Positive Metastatic Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial. Huober, J., Weder, P., Ribi, K., et al.[2023]

In a study of 92 patients with stage II or III HER2+ breast cancer receiving neoadjuvant therapy with paclitaxel, trastuzumab, and pertuzumab, 55.4% were able to undergo breast conservation therapy (BCT), indicating the effectiveness of this treatment approach in increasing BCT eligibility.

Of the patients initially ineligible for BCT, 78.6% became eligible after treatment, and 81.8% of those eligible actually underwent BCT, highlighting the potential of neoadjuvant therapy to significantly improve treatment options for patients with larger tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of Neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab on Breast Tumor Downsizing for Patients with HER2+ Breast Cancer: Single-Arm Prospective Clinical Trial. Weiss, A., Li, T., Desai, NV., et al.[2023]

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