What is the administration schedule for Pembrolizumab (pembrolizumab) in carcinoma (ca) of the breast?

Pembrolizumab Administration Schedule in Breast Cancer

Pembrolizumab is administered at 200 mg intravenously every 3 weeks in breast cancer, with the specific duration and setting depending on whether it is used in the neoadjuvant, adjuvant, or metastatic setting. 1

Neoadjuvant Setting (Early-Stage Triple-Negative Breast Cancer)

For patients with stage II-III triple-negative breast cancer receiving neoadjuvant therapy:

• Pembrolizumab 200 mg IV every 3 weeks is administered concurrently with chemotherapy for a maximum of 4 cycles preoperatively 1
• The chemotherapy backbone consists of carboplatin plus paclitaxel for 4 cycles, followed by doxorubicin/epirubicin plus cyclophosphamide for 4 cycles, with pembrolizumab given throughout 1, 2
• This regimen is recommended regardless of PD-L1 status for node-positive or high-risk triple-negative breast cancer 3

Adjuvant Setting (Post-Surgery Continuation)

After definitive surgery, patients continue pembrolizumab:

• Pembrolizumab 200 mg IV every 3 weeks for 9 additional cycles (or up to 1 year total from start of neoadjuvant therapy) 1, 3
• This adjuvant continuation is recommended regardless of whether pathologic complete response was achieved 3
• The total treatment duration from neoadjuvant through adjuvant phases should not exceed 2 years 1

Metastatic Setting

First-Line Metastatic Triple-Negative Breast Cancer (with PD-L1 CPS ≥10)

For patients with untreated metastatic triple-negative breast cancer and PD-L1 combined positive score ≥10:

• Pembrolizumab 200 mg IV every 3 weeks in combination with chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin) 1
• Treatment continues until disease progression, unacceptable toxicity, or completion of 2 years (approximately 35 cycles) 1, 4
• The KEYNOTE-355 trial demonstrated median PFS of 9.7 months with this regimen versus 5.6 months with chemotherapy alone in the PD-L1 CPS ≥10 population 1

Previously Treated Metastatic Disease

Pembrolizumab monotherapy is NOT recommended for previously treated metastatic triple-negative breast cancer based on the KEYNOTE-119 trial, which showed no overall survival benefit (median OS 9.9 months with pembrolizumab vs 10.8 months with chemotherapy, HR 0.97) 4

Special Indications (Tumor-Agnostic)

MSI-H/dMMR Metastatic Breast Cancer

For patients with microsatellite instability-high or mismatch repair deficient tumors who have progressed after prior treatment:

• Pembrolizumab 200 mg IV every 3 weeks for up to 2 years 1
• This indication applies only when no satisfactory alternative treatment options exist 1
• The KEYNOTE-158 trial showed an objective response rate of 34.3% with median PFS of 4.1 months in MSI-H/dMMR solid tumors 1

Critical Dosing Details

The standard dose across all breast cancer indications is consistently 200 mg IV every 3 weeks, which differs from some other malignancies where alternative schedules (240 mg every 2 weeks or 400 mg every 6 weeks) may be used 1

Common Pitfalls to Avoid

• Do not delay pembrolizumab administration beyond 3 weeks without clinical justification, as the pharmacokinetic profile is optimized for this schedule 1
• Do not omit the adjuvant pembrolizumab cycles after achieving pathologic complete response in the neoadjuvant setting, as the KEYNOTE-522 trial included completion of all planned cycles regardless of surgical pathology 1, 3
• Do not use pembrolizumab monotherapy in previously treated metastatic triple-negative breast cancer outside of MSI-H/dMMR tumors, as it showed no survival benefit in KEYNOTE-119 4
• Do not initiate pembrolizumab in metastatic triple-negative breast cancer without first confirming PD-L1 status using the FDA-approved 22C3 companion assay, as benefit is restricted to CPS ≥10 1

Biomarker Testing Requirements

Before initiating pembrolizumab in metastatic triple-negative breast cancer:

• PD-L1 testing using the 22C3 companion diagnostic assay is mandatory 1
• The assay calculates a combined positive score (CPS), which includes PD-L1 staining on tumor cells, lymphocytes, and macrophages divided by total viable tumor cells, multiplied by 100 1
• CPS ≥10 is required for pembrolizumab plus chemotherapy in first-line metastatic disease 1