Pembrolizumab vs. Observation in People With Triple-negative Breast Cancer Who Had a Pathologic Complete Response After Chemotherapy Plus Pembrolizumab
Anatomic Stage II Breast Cancer AJCC v8Early Stage Triple-Negative Breast CarcinomaAnatomic Stage IIIA Breast Cancer AJCC v8Anatomic Stage IIIB Breast Cancer AJCC v8
Biospecimen Collection: Undergo collection of blood
Questionnaire Administration: Ancillary studies
Quality-of-Life Assessment: Ancillary studies
Study summary
This phase III trial compares the effect of continuation of treatment with pembrolizumab (usual approach) to observation only at preventing cancer from coming back in patients with early-stage triple-negative breast cancer (TNBC) who achieved a pathologic complete response after preoperative chemotherapy in combination with pembrolizumab. The usual approach for patients with early-stage TNBC who receive preoperative chemotherapy plus pembrolizumab is to continue to receive pembrolizumab for up to 27 weeks after surgery. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help researchers determine if observation is as good as receiving pembrolizumab for 27 weeks after surgery in triple-negative breast cancer patients who achieved a pathologic complete response after preoperative treatment with chemotherapy and pembrolizumab.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
* Triple Negative Breast Cancer:
* Patients with a history of clinical stage T1cN1-2 or T2-4N0-2 (clinical stage II or III prior to preoperative therapy) breast cancer at time of diagnosis according to the primary tumor-regional lymph node anatomic staging criteria of the American Joint Committee on Cancer (AJCC), 8th edition as determined by the investigator in radiologic assessment, clinical assessment or both
* Patients must have no residual invasive disease in the breast or lymph nodes after the completion of neoadjuvant therapy. Residual ductal carcinoma in situ (DCIS) is allowed. Isolated tumor cells are considered node-negative
* Estrogen receptor (ER) and progesterone receptor (PR) =\< 10%; HER2-negative by American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines (immunohistochemistry \[IHC\] and fluorescence in situ hybridization \[FISH\])
* If invasive disease was present in both breasts, participation in the study is permitted as long as the eligibility criteria are met for both tumors/breasts
* Patients must have received neoadjuvant chemotherapy in combination with pembrolizumab for a minimum of 6 cycles. All systemic chemotherapy must have been completed preoperatively
* An interval of no more than 12 weeks between the completion date of the final surgery and the date of randomization
\* Note: Adjuvant radiation can be given on study, however, it is recommended to complete adjuvant radiation prior to registration. If radiation is given on study, it is encouraged to be given concurrently with pembrolizumab if the patient is on the pembrolizumab arm, per investigator discretion. Treatment with adjuvant pembrolizumab is strongly discouraged prior to participation in this trial, but if administered (e.g., if patients are awaiting pathology results), pembrolizumab may be administered for up to 6 weeks (i.e., up to 2 q3week doses or up to one q6week dose) post-surgery and must be completed prior to registration post-surgery and must be completed prior to registration
* Use of investigational anti-cancer agents must be discontinued at time of registration
* Adequate excision: Surgical removal of all clinically evident disease in the breast and lymph nodes as follows:
* Breast surgery: Total mastectomy or breast-conserving surgery with histologically negative margins, including no ink on tumor for DCIS, at the time of excision
\*\* For patients who undergo breast-conserving surgery, the margins of the resected specimen must be histologically free of ductal carcinoma in-situ (DCIS) as determined by the local pathologist. If pathologic examination demonstrates DCIS at the line of resection, additional operative procedures may be performed to obtain clear margins. If DCIS is still present at the resected margin after re-excision(s), the patient must undergo total mastectomy to be eligible. Patients with margins positive for classic lobular carcinoma in situ (LCIS) are eligible without additional resection
* Lymph node surgery:
* For a patient with clinically N0 disease, a sentinel lymph node biopsy should have been performed at time of surgical evaluation, and if pathologically node positive, the patient is no longer eligible. Isolated tumor cells are considered node-negative
* For a patient with clinically N1 disease at diagnosis (with positive results from a fine-needle aspiration, core biopsy, or sentinel node biopsy performed prior to preoperative therapy) additional surgical evaluation of the axilla following preoperative therapy is required
\*\*\* If they become cN0 (no palpable adenopathy), then a sentinel lymph node biopsy could have been performed at time of surgery (axillary dissection would also be permitted); if the sentinel lymph node biopsy is positive, the patient is no longer eligible
* If sentinel node biopsy performed before preoperative therapy was negative, no additional surgical evaluation of the axilla is required after preoperative therapy. If sentinel node biopsy performed before preoperative therapy was positive, an ALND is required after preoperative therapy
* If the only sentinel node identified by isotope scan is in the internal mammary chain, surgical evaluation of the axilla is still required
* If sentinel node evaluation after preoperative therapy is negative, no further additional surgical evaluation of the axilla is required
* Axillary dissection without sentinel node evaluation is permitted as the initial or sole axillary evaluation after preoperative therapy
* If breast-conserving surgery was performed but patient will not be receiving breast radiation, the patient is not eligible
* Not pregnant and not nursing, because this study involves an agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown. Therefore, for women of childbearing potential only, a negative serum or urine pregnancy test done =\< 7 days prior to randomization is required
* Absolute neutrophil count (ANC) \>= 1,000/mm\^3
* Platelet Count \>= 100,000/mm\^3
* Estimated glomerular filtration rate (eGFR) \>= 15 mL/min/1.73m\^2
* Total Bilirubin =\<1.5 x upper limit of normal (ULN)
\* Patients with Gilbert's disease with a total bilirubin =\< 2.5 x ULN and direct bilirubin within normal limits are permitted
* Aspartate aminotransferase (AST) serum aspartate aminotransferase \[SGOT\] / alanine aminotransferase (ALT) serum glutamic pyruvic transaminase \[SGPT\] =\< 3 x institutional ULN
* Patients must be willing to provide tumor tissue from the diagnostic core biopsy. If inadequate tumor tissue is available, patients are still eligible to participate in the trial
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
* Patients with known HIV infection who are on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration are eligible for this trial
Exclusion Criteria:
* No stage IV (metastatic) breast cancer
* No history of any prior (ipsi- or contralateral) invasive breast cancer. Prior DCIS is allowed
* No evidence of recurrent disease following preoperative therapy and surgery
* No known active liver disease, e.g. due to hepatitis B virus (HBV), hepatitis C virus (HCV), autoimmune hepatic disorders, or sclerosing cholangitis
* No history of intolerance, including Grade 3 or 4 infusion reaction or hypersensitivity to pembrolizumab or murine proteins or any components of the product
\* Note: Prior immune-related adverse events (irAEs) are allowed if they resolved to ≤ grade 1 and the patient tolerated subsequent therapy without requiring chronic steroids for the irAE. The following are exceptions to this criterion: Grade 2 or lower immune mediated endocrinopathies due to neoadjuvant checkpoint inhibition but patients are stable on endocrine therapy and were able to continue checkpoint inhibition.
* No medical conditions that require chronic systemic steroids (\>10 mg prednisone daily or equivalent) or any other form of immunosuppressive medications and has required such therapy in the last two years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic therapy
* Patients who are unable or unwilling to comply with the requirements of the protocol per investigator assessment are not eligible
Primary outcome measure(s)
Recurrence-free survival (RFS) — Up to 10 years. Defined as the time from randomization to first invasive local, regional, or distant recurrence or death due to any cause. RFS will be compared between treatment arms using the hazard ratio (with 90% confidence interval and stratified log-rank test) from a stratified Cox model.
Trial sites (846)
Facility
City
Region
Status
University of Alabama at Birmingham Cancer Center
Birmingham
Alabama
Active Not Recruiting
Thomas Hospital
Fairhope
Alabama
Recruiting
Mobile Infirmary Medical Center
Mobile
Alabama
Recruiting
University of South Alabama Mitchell Cancer Institute
Mobile
Alabama
Recruiting
Katmai Oncology Group
Anchorage
Alaska
Recruiting
CTCA at Western Regional Medical Center
Goodyear
Arizona
Recruiting
Kingman Regional Medical Center
Kingman
Arizona
Recruiting
Cancer Center at Saint Joseph's
Phoenix
Arizona
Recruiting
Mayo Clinic Hospital in Arizona
Phoenix
Arizona
Recruiting
Highlands Oncology Group - Fayetteville
Fayetteville
Arkansas
Recruiting
NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro
Jonesboro
Arkansas
Recruiting
University of Arkansas for Medical Sciences
Little Rock
Arkansas
Recruiting
Highlands Oncology Group - Rogers
Rogers
Arkansas
Recruiting
Highlands Oncology Group
Springdale
Arkansas
Recruiting
Mission Hope Medical Oncology - Arroyo Grande
Arroyo Grande
California
Recruiting
PCR Oncology
Arroyo Grande
California
Recruiting
Alta Bates Summit Medical Center-Herrick Campus
Berkeley
California
Recruiting
Tower Cancer Research Foundation
Beverly Hills
California
Recruiting
Marshall Cancer Center
Cameron Park
California
Recruiting
Mercy Cancer Center - Carmichael
Carmichael
California
Recruiting
Mercy San Juan Medical Center
Carmichael
California
Recruiting
Enloe Medical Center
Chico
California
Recruiting
Kaiser Permanente Dublin
Dublin
California
Recruiting
Mercy Cancer Center - Elk Grove
Elk Grove
California
Recruiting
Stanford Cancer Center Emeryville
Emeryville
California
Recruiting
Kaiser Permanente-Fremont
Fremont
California
Recruiting
Kaiser Permanente Fresno Orchard Plaza
Fresno
California
Recruiting
Kaiser Permanente-Fresno
Fresno
California
Recruiting
UCI Health - Chao Family Comprehensive Cancer Center and Ambulatory Care
Irvine
California
Active Not Recruiting
Loma Linda University Medical Center
Loma Linda
California
Recruiting
Cedars-Sinai Medical Center
Los Angeles
California
Recruiting
Fremont - Rideout Cancer Center
Marysville
California
Recruiting
Kaiser Permanente- Modesto MOB II
Modesto
California
Recruiting
Kaiser Permanente-Modesto
Modesto
California
Recruiting
Kaiser Permanente-Oakland
Oakland
California
Recruiting
Saint Joseph Hospital - Orange
Orange
California
Recruiting
UC Irvine Health/Chao Family Comprehensive Cancer Center
Orange
California
Active Not Recruiting
Desert Regional Medical Center
Palm Springs
California
Recruiting
Stanford Cancer Institute Palo Alto
Palo Alto
California
Suspended
Huntington Memorial Hospital
Pasadena
California
Recruiting
+ 806 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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