Carboplatin Use in Neoadjuvant Pembrolizumab Regimens for Triple-Negative Breast Cancer
Carboplatin should be routinely included in the neoadjuvant regimen for stage II/III triple-negative breast cancer when using pembrolizumab, following the KEYNOTE-522 protocol: AC (anthracycline-cyclophosphamide) followed by paclitaxel-carboplatin with concurrent pembrolizumab throughout, then adjuvant pembrolizumab for 9 cycles. 1
Standard Regimen for Stage II/III TNBC
The preferred approach is the KEYNOTE-522 protocol, which includes:
- 4 cycles of paclitaxel + carboplatin + pembrolizumab (given every 3 weeks)
- Followed by 4 cycles of AC or EC + pembrolizumab
- Then adjuvant pembrolizumab for 9 cycles post-surgery 1, 2, 3
This regimen demonstrated superior outcomes with a hazard ratio of 0.63 (95% CI 0.48-0.82, P<0.001) for event-free survival compared to chemotherapy alone. 4 The 36-month event-free survival was 84.5% with pembrolizumab versus 76.8% without it. 4
When Carboplatin is Routinely Indicated
Carboplatin should be standard for:
- All stage II TNBC receiving neoadjuvant pembrolizumab 1
- All stage III TNBC receiving neoadjuvant pembrolizumab 1
- Node-positive disease at presentation 1
- Higher-risk stage I disease (T1c) when pembrolizumab is being considered 2, 3
The benefit from carboplatin is independent of germline BRCA1/2 status, so BRCA mutation status should not influence the decision to include carboplatin. 1
Key Evidence Supporting Routine Carboplatin Use
The St. Gallen 2023 consensus specifically states that "some panelists favor inclusion of carboplatin in neoadjuvant therapy for TNBC, particularly if used in node-positive cancers and in conjunction with pembrolizumab-based treatment." 1 More importantly, recent studies show "reduced risk of recurrence with regimens that incorporate carboplatin in addition to pembrolizumab-based regimen." 1
The KEYNOTE-522 trial, which forms the basis for FDA approval, included carboplatin as part of the standard regimen and demonstrated:
- Pathological complete response rate of 64.8% with pembrolizumab-chemotherapy versus 51.2% with chemotherapy alone (difference 13.6 percentage points, P<0.001) 5
- Benefit regardless of PD-L1 status 1, 6
Pembrolizumab Use Independent of PD-L1
Pembrolizumab should be used regardless of PD-L1 status. 1, 6 The benefit from pembrolizumab is independent of PD-L1 expression, and testing for PD-L1 is not required to determine eligibility for pembrolizumab in early TNBC. 1
Alternative Considerations (When Carboplatin Might Be Omitted)
Carboplatin may potentially be omitted only in:
- Stage I T1a or T1b disease where chemotherapy itself is being used selectively 1, 3
- Patients with contraindications to platinum therapy (severe renal impairment, severe neuropathy, severe cytopenias) 1
However, for any patient receiving the full KEYNOTE-522 protocol with pembrolizumab for stage II/III disease, carboplatin should be included as standard. 1, 2, 3
Critical Implementation Points
- Sequence matters: The KEYNOTE-522 protocol uses paclitaxel-carboplatin-pembrolizumab FIRST, followed by anthracycline-cyclophosphamide-pembrolizumab 5, 4
- Adjuvant pembrolizumab continuation is recommended regardless of pathologic response (pCR or residual disease) 1
- Grade 3-4 treatment-related adverse events occurred in 78-81% of patients, but this was similar between pembrolizumab and placebo groups 7, 5
Common Pitfall to Avoid
Do not omit carboplatin from the pembrolizumab regimen based on BRCA status—the benefit is independent of germline BRCA1/2 mutations. 1 The addition of carboplatin improves pathologic complete response rates and event-free survival when combined with pembrolizumab. 1