Is pembrolizumab (pembrolizumab) considered as an adjuvant therapy for patients with triple-negative breast cancer (TNBC) who have achieved pathologic complete response (pCR)?

Adjuvant Pembrolizumab for TNBC with Pathologic Complete Response

For patients with triple-negative breast cancer (TNBC) who have achieved pathologic complete response (pCR) after neoadjuvant therapy, adjuvant pembrolizumab should still be administered for nine 3-week cycles regardless of pCR status.

Evidence-Based Recommendation

The 2023 St. Gallen International Consensus Conference and 2024 ESMO Clinical Practice Guidelines provide clear direction on this question:

• According to the St. Gallen Consensus, patients with TNBC should receive adjuvant pembrolizumab for nine courses if it was given in the neoadjuvant setting, regardless of the extent of response 1.

• ESMO guidelines explicitly state that pembrolizumab should be administered for nine 3-week cycles during the adjuvant phase, regardless of pCR status 1.

Treatment Algorithm

1. Neoadjuvant Phase:

   • Pembrolizumab 200 mg IV every 3 weeks throughout neoadjuvant chemotherapy
   • Standard chemotherapy regimen (typically sequential anthracycline and taxane-based)

2. Surgery:

   • Definitive surgery after completion of neoadjuvant therapy
   • Assessment of pathologic response

3. Adjuvant Phase:

   • Continue pembrolizumab for nine 3-week cycles regardless of pCR status
   • Monitor closely for immune-related adverse events

Clinical Evidence Supporting This Approach

The recommendation is primarily based on the KEYNOTE-522 trial, which demonstrated significant improvements in both pCR rates and event-free survival (EFS) with the addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab 2.

Recent exploratory analysis of KEYNOTE-522 data showed that:

• Pembrolizumab shifted patients into lower residual cancer burden (RCB) categories
• The addition of pembrolizumab resulted in fewer EFS events across RCB-0 (pCR), RCB-1, and RCB-2 categories 2
• The benefit of adjuvant pembrolizumab was maintained even in patients who achieved pCR

Real-World Evidence

Real-world studies have confirmed the efficacy of the neoadjuvant-adjuvant pembrolizumab approach:

• A Turkish Oncology Group study reported a pCR rate of 63.9% with neoadjuvant pembrolizumab plus chemotherapy, with 2-year EFS of 87.2% 3.

• A multivariate analysis found that completing at least 8 cycles of pembrolizumab was significantly associated with achieving pCR (OR 2.49, P=0.037) 4.

Important Considerations

1. Monitoring for Toxicity:

   • Patients receiving pembrolizumab should be monitored very closely for immune-related adverse events throughout treatment 1
   • Follow established guidelines for management of immunotherapy toxicities

2. Treatment Sequence:

   • Pembrolizumab should not be given solely in the adjuvant setting without prior neoadjuvant immunotherapy 1
   • The complete treatment course (neoadjuvant + adjuvant) is what demonstrated survival benefit

3. Special Populations:

   • The benefit of pembrolizumab appears consistent across subgroups, including Asian populations 5
   • Benefit is observed regardless of PD-L1 status

Conclusion

Despite achieving pCR, TNBC patients who received neoadjuvant pembrolizumab should complete the full course of adjuvant pembrolizumab for nine 3-week cycles to maximize the reduction in recurrence risk and improve survival outcomes.