Pembrolizumab Shows Early Triple-Negative Breast Cancer Potential

Author:  By Lynda Williams, Senior medwireNews Reporter

medwireNews: Adding pembrolizumab to neoadjuvant chemotherapy improves the pathological complete response rate (pCR) for women with early-stage triple-negative breast cancer (TNBC), suggest KEYNOTE-522 trial findings reported at the ESMO 2019 Congress in Barcelona, Spain.  

Presenting author Peter Schmid, from Barts Cancer Institute in London, UK, outlined the trial design, explaining that patients with T1c node-positive or T2-4 node-unevaluated TNBC were randomly assigned to receive pembrolizumab or placebo alongside a neoadjuvant chemotherapy regimen consisting of cisplatin plus paclitaxel followed by doxorubicin or epirubicin with cyclophosphamide. 

Patients either then continued pembrolizumab therapy after surgery or received placebo in this maintenance phase, he continued. 

The primary endpoint of pCR – defined as no evidence of residual tumour in the breast or lymph nodes – was achieved by 64.8% of pembrolizumab-treated patients and 51.2% of controls, a 13.6% difference that was highly statistically significant, Peter Schmid reported. 

Overall, 83% of patients were PD-L1-positive with a combined positive score of 1 or more. These individuals were significantly more likely to achieve a pCR with pembrolizumab than with placebo (68.9 vs 54.9%), and this was also true for the patients with no PD-L1 expression (45.3 vs 30.3%).  

Pembrolizumab therapy was also associated with a trend towards a lower rate of disease events than placebo, at 7.4% versus 11.8%. Schmid told medwireNews that although this difference did not reach statistical significance at this early analysis, after a median follow-up of 15 months, “the early signs for event-free survival are hugely encouraging”. The estimated 18-month rates of event-free survival were 91.3% versus 85.3%, respectively. 

Treatment-related adverse events in the trial were “manageable and consistent” with the known toxicity profiles for chemotherapy and pembrolizumab, and grade 3–5 events were low in both the pembrolizumab and placebo groups in the adjuvant phase, affecting 5.7% and 1.9%, respectively. Discontinuation because of adverse events occurred in a corresponding 3.3% and 1.3% of patients. 

“The KEYNOTE-522 trial is the first phase III trial that demonstrates a clear benefit with immune therapy in early TNBC”, Schmid said. 

“The trial, in my opinion, has clearly the potential to be practice changing and we will have to decide in the community whether it already is or whether we require longer follow-up before we make that final call”, he concluded. 

Reference  

Schmid P, Cortés J, Dent R, et al. KEYNOTE-522: Phase III study of pembrolizumab (pembro) + chemotherapy (chemo) vs placebo (pbo) + chemo as neoadjuvant treatment, followed by pembro vs pbo as adjuvant treatment for early triple-negative breast cancer (TNBC). ESMO 2019 Congress; Barcelona, Spain: 27 September–1 October. LBA8_PR