Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Early Triple Negative Breast Cancer

Summary

Objectives

PRIMARY OBJECTIVE:
I. To assess whether participants with early stage triple negative breast cancer (TNBC) randomized to receive anthracycline-free, taxane-platinum neoadjuvant chemotherapy with pembrolizumab have non-inferior breast cancer event-free survival (BC-EFS) compared to participants randomized to taxane-platinum-anthracycline neoadjuvant chemotherapy with pembrolizumab.

SECONDARY OBJECTIVES:
I. To compare pathological complete response (pCR) and residual cancer burden (RCB) rates by randomized arm.
II. To compare pCR and RCB rates between randomized arms by tumor infiltrating lymphocytes (TIL) status.
III. To compare BC-EFS between randomized arms in the TIL-enriched and non-TIL enriched subgroups.
IV. To compare distant relapse-free survival and overall survival by randomized arm.
V. To compare invasive breast cancer-free survival after surgery between randomized arms in pCR and residual disease groups.
VI. To compare the safety and tolerability by randomized arm among those that initiate therapy.

TRANSLATIONAL MEDICINE OBJECTIVE:
I. To evaluate concordance and accuracy of an automated stromal TIL (sTIL) algorithm versus (vs.) central pathologist assessed sTILs quantification.

PATIENT REPORTED OUTCOME (PRO) OBJECTIVES:
I. To compare patient-reported fatigue at 3 weeks after the last neoadjuvant systemic therapy (NAST) dose and, separately, at 18 months after randomization, using the Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue-7a in participants undergoing NAST with taxane-platinum-anthracycline chemo-immunotherapy vs taxane-platinum chemo-immunotherapy. (Quality of Life, Primary)
II. To compare physical function experienced by participants undergoing neoadjuvant systemic chemotherapy (NAST) with taxane-platinum-anthracycline chemo-immunotherapy vs taxane-platinum chemo-immunotherapy, within 3-5 weeks post last neoadjuvant systemic therapy dose using the PROMIS-29 Profile physical function subscale score. (Quality of Life, Secondary)
III. To compare physical function experienced by participants undergoing NAST taxane-platinum-anthracycline chemo-immunotherapy vs taxane-platinum chemo-immunotherapy at 18 months post registration using the PROMIS-29 Profile physical function subscale score. (Quality of Life, Secondary)
IV. To compare other PROMIS-29 Profile subscale scores (sleep disturbance, depression, anxiety, social, pain interference, and pain sensitivity) and GP5 question response by arm within 3-5 weeks post last neoadjuvant systemic therapy dose and at 18 months post registration. (Quality of Life, Exploratory)
V. To compare the GP-5 item scores by arm within 3-5 weeks post last neoadjuvant systemic therapy dose and at 18 months post registration. (Quality of Life, Exploratory)
VI. To compare select patient-reported outcomes using the Common Terminology Criteria for Adverse Events (PRO-CTCAE) by arm. (Patient-Reported Symptoms of Treatment)

BANKING OBJECTIVE:
I. To bank physical specimens and digital slides for future correlative studies.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive paclitaxel intravenously (IV) over 60 minutes on days 1, 8, and 15 and carboplatin IV on day 1 or days 1, 8, and 15 of cycles 1-4. Patients also receive pembrolizumab IV on day 1 of cycles 1-8 and doxorubicin IV over 3-5 minutes and cyclophosphamide IV over 30 minutes on day 1 of cycles 5-8. Treatment repeats every 14 or 21 days (per treating physician discretion) for a total of 8 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. Patients may receive pembrolizumab with/without capecitabine chemotherapy after surgery. Patients may optionally undergo collection of blood samples throughout the trial.

ARM II: Patients receive docetaxel IV over 60 minutes, carboplatin IV, and pembrolizumab IV on day 1 of each treatment cycle. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. Patients may receive pembrolizumab with/without chemotherapy with doxorubicin and cyclophosphamide after surgery. Patients may optionally undergo collection of blood samples throughout the trial.

Patients are followed up every 6 months for the first 2 years and then annually until 5 years from registration.