Neoadjuvant Pembrolizumab Combo Prolongs pCR in Phase III TNBC Study

Results from the pivotal neoadjuvant/adjuvant Phase 3 KEYNOTE-522 trial in patients with early-stage triple-negative breast cancer (TNBC) were announced at ESMO2019. The trial investigated a regimen of neoadjuvant pembrolizumab (KEYTRUDA) plus chemotherapy, followed by adjuvant pembrolizumab as monotherapy compared with a regimen of neoadjuvant chemotherapy followed by adjuvant placebo (the chemotherapy-placebo regimen). Interim findings – which are from the first randomized trial of an anti-PD-1 therapy in the neoadjuvant/adjuvant setting for TNBC.

In the neoadjuvant phase, pembrolizumab plus chemotherapy (n=401) resulted in a statistically significant increase in pathological complete response (pCR) versus chemotherapy (n=201), from 51.2% with neoadjuvant chemotherapy to 64.8% for neoadjuvant pembrolizumab plus chemotherapy, in patients with early-stage TNBC (p=0.00055). Pathological complete response, one of the dual primary e ndpoints was defined as ypT0/Tis ypN0 (i.e., no invasive residual cancer in breast and lymph nodes). The improvement seen when adding pembrolizumab to neoadjuvant chemotherapy was observed regardless of PD-L1 expression. In the other dual primary endpoint of event-free-survival (EFS), with a median follow-up of 15.5 months, the pembrolizumab regimen reduced the risk of progression in the neoadjuvant phase and recurrence in the adjuvant phase by 37% – a favorable trend for EFS – compared with the chemotherapy-placebo regimen (HR=0.63 [95% CI, 0.43-0.93]). The safety profiles of pembrolizumab and chemotherapy in KEYNOTE-522 were consistent with previous studies.

“As an oncologist specializing in the treatment of TNBC, I am highly encouraged by the significant improvement in pCR rates with KEYTRUDA plus chemotherapy in the neoadjuvant setting and the positive trend for event free-survival demonstrated in this trial,” said Dr. Peter Schmid, lead, Centre for Experimental Cancer Medicine, Barts Cancer Institute. “There is significant need for new treatment regimens that can increase pCR rates in this patient population.”

Pembrolizumab (KEYTRUDA) plus chemotherapy was granted Breakthrough Therapy designation by the FDA for the neoadjuvant treatment of patients with high-risk, early-stage TNBC, based on data from Phase 1b KEYNOTE-173 and Phase 2 I-SPY2 trial. Data demonstrated encouraging anti-tumor activity with neoadjuvant pembrolizumab plus chemotherapy in these patients.

“These findings from the KEYNOTE-522 trial are exciting for the TNBC community – a community in particular need of scientific advances,” said Hayley Dinerman, executive director, Triple Negative Breast Cancer Foundation. “We are committed to supporting patients with TNBC, and we are pleased to see new data focused on earlier lines of treatment.”