- Pembrolizumab significantly increased pathological complete response (pCR) when added to neoadjuvant chemotherapy and continued as adjuvant maintenance.
- Pembrolizumab also showed a favourable effect on event-free survival (EFS).
- Longer follow-up is needed to definitively assess benefit.
Why this matters
- pCR (absence of detectable residual cancer cells) is an accepted endpoint for accelerated drug approval in TNBC.
- With chemotherapy, TNBC patients with pCR have an 85-90% likelihood of nonrecurrence, falling to 40-50% with residual viable tumour tissue.
- pCR increased from 51.2% (95% CI 44.1–58.3) in the placebo group to 64.8% (95% CI 59.9–69.5) with pembrolizumab (P=0.00055), a 13.6% difference described as clinically meaningful.
- Early EFS favoured pembrolizumab (hazard ratio 0.63, 95% CI 0.43–0.93), but longer follow-up is needed.
- Grade ≥3 treatment-related adverse events occurred in 78.0% and 73.0% of the pembrolizumab and placebo groups, respectively.
- Patients with previously untreated, nonmetastatic TNBC (stage T1c N1-2 or T2-4 N0-2) were randomised 2:1 to pembrolizumab 200 mg every 3 weeks or placebo, both given with 4 cycles of paclitaxel+carboplatin, then with 4 cycles of doxorubicin or epirubicin+cyclophosphamide (neoadjuvant phase).
- After definitive surgery, patients received pembrolizumab or placebo for 9 cycles or until recurrence or unacceptable toxicity (adjuvant phase).
- The primary endpoints were pCR and EFS.
- Funding: MSD.
- “I have no doubt that checkpoint inhibitors will help us treat patients with early TNBC better, but we need to wait for more mature EFS data and improved patient selection,” said invited discussant Professor Sherene Loi (Peter MacCallum Cancer Centre, Victoria, Australia), who was not involved in the study. “Not all early-stage TNBC patients will need this therapy, and we do not yet know how pCR translates to EFS with immunotherapy. More follow-up on immune-related adverse events is also needed.”