Pembrolizumab (Keytruda, Merck) plus chemotherapy led to an increased pathological complete response (pCR) compared with chemotherapy alone in patients with triple-negative breast cancer (TNBC), according to results released by the pivotal neoadjuvant/adjuvant phase 3 KEYNOTE-522 trial. The interim findings were presented at the ESMO Congress 2019 in Barcelona, Spain.

The trial investigated a regimen of neoadjuvant pembrolizumab, an anti-PD-1 therapy, plus chemotherapy, followed by adjuvant pembrolizumab monotherapy compared with a regimen of neoadjuvant chemotherapy followed by adjuvant placebo.

Researchers randomized patients with TNBC in a 2:1 ratio to receive a 200 mg dose of pembrolizumab every 3 weeks (n=784) or placebo (n=390). Patients received 4 cycles of carboplatin plus paclitaxel followed by 4 cycles of doxorubicin or epirubicin plus cyclophosphamide. Following surgery, adjuvant pembrolizumab was continued for 9 cycles or until disease recurrence or unacceptable toxicity.

In the neoadjuvant phase, pembrolizumab plus chemotherapy resulted in a statistically significant increase in pCR versus chemotherapy, from 51.2% with neoadjuvant chemotherapy to 64.8% for neoadjuvant pembrolizumab plus chemotherapy, in patients with early-stage TNBC. Researchers saw an improvement in pCR when they added pembrolizumab to neoadjuvant chemotherapy regardless of PD-L1 expression.

In an exploratory sub-group analysis of pCR based on PD-L1 expression, the pCR rate was 68.9% compared with 54.9% for pembrolizumab and placebo.

The FDA granted breakthrough therapy designation for Keytruda plus chemotherapy for the neoadjuvant treatment of patients with high-risk, early-stage TNBC.

Merck plans to share early interim analysis data from Keynote-522 with regulatory authorities.

  1. Merck’s KEYTRUDA® (pembrolizumab) Plus Chemotherapy Showed Statistically Significant Increase in Pathological Complete Response Versus Chemotherapy as Neoadjuvant Therapy in Early-Stage Triple-Negative Breast Cancer (TNBC) [press release]. Merck website. Published September 29, 2019. Accessed September 30, 2019.