From the Guidelines
Pembrolizumab is recommended for triple-negative breast cancer (TNBC) as neoadjuvant therapy with chemotherapy, followed by adjuvant pembrolizumab for a total treatment duration of approximately one year, as stated in the most recent guideline from 2024 1.
Key Points
- Pembrolizumab should be administered every 3 weeks throughout the neoadjuvant phase and for nine 3-week cycles during the adjuvant phase, regardless of pCR status 1.
- The use of dose-dense schedules of chemotherapy, with granulocyte colony-stimulating factor support, should be considered given their documented benefit over non-dose-dense schedules 1.
- Patients receiving pembrolizumab should be monitored very closely for the risk of immune-related adverse events throughout treatment and following the ESMO CPG for the management of toxicities from immunotherapy 1.
- For high-risk early-stage TNBC, neoadjuvant treatment is preferred, and pembrolizumab can be given in combination with chemotherapy, unless there are risk factors for excessive ICI-associated immune toxicity 1.
Treatment Considerations
- The combination of ICIs and olaparib may be considered on an individual basis, but the combination of olaparib and capecitabine in patients with gBRCAm should not be used 1.
- Patients with residual disease who did not receive ICIs should be offered adjuvant capecitabine for 6-8 cycles 1.
- The ESMO-MCBS v1.1 score and ESCAT scores can be used to guide treatment decisions, with a score of A indicating a high level of evidence and a strong recommendation for treatment 1.
Monitoring and Follow-up
- Patients should be monitored for immune-related adverse events, including pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions 1.
- Treatment should be continued until disease progression, unacceptable toxicity, or completion of planned therapy 1.
From the Research
Pembrolizumab in Breast Cancer
- Pembrolizumab has been studied in combination with chemotherapy for the treatment of advanced triple-negative breast cancer, with results showing longer progression-free survival and overall survival compared to chemotherapy alone in patients with tumors expressing PD-L1 with a combined positive score (CPS) of 10 or more 2.
- A systematic review and network meta-analysis found that pembrolizumab plus chemotherapy was statistically superior to other immunotherapy- or chemotherapy-based treatment regimens for the first-line treatment of locally recurrent unresectable or metastatic triple-negative breast cancer 3.
- Pembrolizumab has also been investigated in the neoadjuvant setting for high-risk, early-stage triple-negative breast cancer, with results showing a significant improvement in pathologic complete response rate and 3-year event-free survival compared to neoadjuvant chemotherapy alone 4.
Efficacy and Safety
- The addition of pembrolizumab to chemotherapy has been shown to result in significantly longer overall survival than chemotherapy alone in patients with advanced triple-negative breast cancer whose tumors express PD-L1 with a CPS of 10 or more 2.
- The safety profile of pembrolizumab plus chemotherapy has been evaluated in several studies, with common adverse events including neutropenia, febrile neutropenia, and immune-mediated adverse events 2, 5.
- The impact of pembrolizumab on ovarian function in young triple-negative breast cancer patients treated with chemo-immunotherapy has been evaluated, with results showing no additional impact of pembrolizumab on anti-Müllerian hormone (AMH) evolution compared to chemotherapy alone 6.
Biomarkers and Correlates
- Tumor PD-L1 expression and stromal tumor-infiltrating lymphocyte (sTIL) levels have been identified as potential biomarkers for response to pembrolizumab in triple-negative breast cancer 2, 5.
- Higher pre-treatment PD-L1 combined positive score and pre- and on-treatment sTILs have been significantly associated with higher pathologic complete response rates in patients treated with pembrolizumab plus chemotherapy 5.