Title
OptimICE-PCR: De-Escalation of Therapy in Early-Stage TNBC Patients Who Achieve pCR After Neoadjuvant Chemotherapy with Checkpoint Inhibitor Therapy

Description
The phase III trial compares the effect of pembrolizumab to observation for the treatment of patients with early-stage triple-negative breast cancer who achieved a pathologic complete response after preoperative chemotherapy in combination with pembrolizumab. 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 will result in the same risk of cancer coming back as pembrolizumab after surgery in triple-negative breast cancer patients who achieve pathologic complete response after preoperative chemotherapy with pembrolizumab.

Objective
PRIMARY OBJECTIVES:

I. To evaluate whether observation results in a non-inferior recurrence-free survival (RFS) compared to adjuvant pembrolizumab in early-stage triple-negative breast cancer (TNBC) patients who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy with pembrolizumab.

II. To compare quality of life (QOL) at approximately 27 weeks as assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B) Trial Outcome Index between patients randomized to adjuvant pembrolizumab versus observation. (Quality of Life) III. To assess the social value of de-escalation of adjuvant breast cancer immunotherapy at approximately 27 weeks and, by modeling, over a lifetime. (Value of Care)

SECONDARY OBJECTIVES:

I. To evaluate whether observation compared to adjuvant pembrolizumab impacts the following:

Ia. RFS by stage at presentation and by receipt of prior anthracycline therapy; Ib. Adverse event rate: difference in Grade 3 or higher adverse event rates overall and Grade 3 or higher immune-related adverse events (irAEs) rates; Ic. Overall Survival (OS); Id. Locoregional recurrence (LRR both isolated LRR as first events and LRR events simultaneous with DM); Ie. RFS, LRR, OS, adverse events, and QOL by age (=< 45, 46-65, and > 65), race, and ethnicity; If. Adverse events related to receipt of radiotherapy. II. To assess the value of de-escalation of breast cancer immunotherapy from the payer perspective at approximately 27 weeks and, by modelling, over a lifetime. (Value of Care) III. To compare patient out-of-pocket costs at approximately 27 weeks between patients randomized to adjuvant pembrolizumab versus observation. (Value of Care) IV. To compare financial toxicity at approximately 27 weeks between patients randomized to adjuvant pembrolizumab versus observation. (Value of Care) V. To compare work/productivity impairment at approximately 27 weeks between patients randomized to adjuvant pembrolizumab versus observation. (Value of Care)

EXPLORATORY OBJECTIVES:

I. To describe trajectories of QOL over time among patients randomized to adjuvant pembrolizumab versus (vs.) observation. (Quality of Life) II. To compare various QOL domains after approximately 27 weeks as assessed by the 5 subscales of the FACT-B Index between patients randomized to adjuvant pembrolizumab versus observation. (Quality of Life) III. To compare self-reported symptomatic adverse events at approximately 27 weeks assessed by the patient reported outcome Common Terminology Criteria for Adverse Events (PRO-CTCAE) between patients randomized to adjuvant pembrolizumab versus observation. (Quality of Life) IV. To describe trajectories of financial toxicity and work/productivity impairment over time from baseline to approximately 27 weeks among patients randomized to adjuvant pembrolizumab versus observation. (Value of Care) V. To develop and assess a measure of value from the patient perspective at approximately 27 weeks. (Value of Care)

Treatment Active Comparator: Arm I (pembrolizumab)
Patients receive pembrolizumab IV on study. Patients also undergo tumor biopsy on study, and collection of blood on study and during follow-up.
Biological: Pembrolizumab
Given IV
Other Name: Keytruda

Procedure: Biopsy
Undergo biopsy

Procedure: Biospecimen Collection
Undergo collection of blood

Other: Questionnaire Administration
Ancillary studies

Other: Quality-of-Life Assessment
Ancillary studies

Experimental: Arm II (observation)
Patients undergo observation on study. Patients also undergo tumor biopsy on study, and collection of blood on study and during follow-up.
Other: Patient Observation
Undergo observation
Other Names:
Active surveillance
watchful waiting
observation

Procedure: Biopsy
Undergo biopsy

Procedure: Biospecimen Collection
Undergo collection of blood

Other: Questionnaire Administration
Ancillary studies

Other: Quality-of-Life Assessment
Ancillary studies

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Breast

Participating Institutions
Johnson Creek, UW Cancer Center; Mercy Health Systems, Janesville ; UW Health 1 S. Park Medical Center; UW Health Carbone Cancer Center Rockford; UW Health Eastpark Medical Center; UW Health University Hospital