A regimen of neoadjuvant pembrolizumab plus chemotherapy, followed by adjuvant pembrolizumab as monotherapy, led to an increased pathological complete response.
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.