Pembrolizumab versus Observation in Patients with Early Stage Triple-Negative Breast Cancer who had a Pathologic Complete Response after Chemotherapy plus Pembrolizumab, OptimICE-PCR Trial

Summary

Objectives

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 distant metastasis [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)

OUTLINE: Patients are randomized to 1 of 2 arms after completing neoadjuvant chemotherapy in combination with pembrolizumab, followed by definitive breast surgery.

ARM I (PEMBROLIZUMAB): Patients receive pembrolizumab intravenously (IV) on study once every 3 weeks (Q3W) or once every 6 weeks (Q6W) for 27 weeks. Patients also undergo tumor biopsy on study, and collection of blood on study and during follow-up. Patients also undergo mammogram, breast ultrasound or magnetic resonance imaging (MRI) during follow-up.

ARM II (OBSERVATION): Patients undergo observation on study for 27 weeks. Patients also undergo tumor biopsy on study, and collection of blood on study and during follow-up. Patients also undergo mammogram, breast ultrasound or MRI during follow-up.

Patients will be followed every 6 months for 5 years after registration or recurrence. Thereafter, patients will be followed annually for overall survival for a total of 10 years after registration.