Keytruda + Chemotherapy showed statistically significant increase in pathological complete response versus chemotherapy as neoadjuvant therapy in early-stage triple-negative breast cancer.- Merck Inc.

Merck has announced results from the pivotal neoadjuvant/adjuvant Phase III KEYNOTE-522 trial in patients with early-stage triple-negative breast cancer (TNBC) . The trial investigated a regimen of neoadjuvant Keytruda, Merck�s anti-PD-1 therapy, plus chemotherapy, followed by adjuvant Keytruda as monotherapy (the Keytruda regimen) 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 � are being presented during the Presidential Symposium at the European Society for Medical Oncology (ESMO) 2019 Congress (Abstract #LBA8).

In the neoadjuvant phase , Keytruda 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 Keytruda plus chemotherapy, in patients with early-stage TNBC (p=0.00055). Pathological complete response, one of the dual primary endpoints was defined as ypT0/Tis ypN0 (i.e., no invasive residual cancer in breast and lymph nodes). The improvement seen when adding Keytruda 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 Keytruda 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 Keytruda and chemotherapy in KEYNOTE-522 were consistent with previous studies.

In an exploratory sub-group analysis of pCR based on PD-L1 expression the improvement seen when adding Keytruda to neoadjuvant chemotherapy was observed regardless of PD-L1 expression. In the PD-L1 CPS ?1 subgroup, the rates of pCR were 68.9% for neoadjuvant Keytruda plus chemotherapy (n=334) versus 54.9% for neoadjuvant chemotherapy (n=164). In the PD-L1 CPS<1 subgroup, the rates of pcr were 45.3% for neoadjuvant keytruda plus chemotherapy (n="64)" versus 30.3% versus neoadjuvant chemotherapy (n="33).">

During the neoadjuvant phase , treatment-related adverse events (TRAEs) of any grade occurred in 99.0% of patients receiving Keytruda plus chemotherapy (n=781) and 99.7% of patients receiving chemotherapy (n=389). Grade 3-5 TRAEs occurred in 76.8% of patients receiving Keytruda plus chemotherapy and 72.2% of patients receiving chemotherapy. The most common Grade 3-5 TRAEs (occurring in ?10% of patients) were neutropenia (34.6%), decreased neutrophil count (18.7%), anemia (18.2%), and febrile neutropenia (17.7%) for KeytrudaA plus chemotherapy and neutropenia (33.2%), decreased neutrophil count (23.1%), and anemia (14.9%) for chemotherapy. TRAEs resulting in discontinuation of any treatment occurred in 23.3% of patients receiving Keytruda plus chemotherapy and 12.3% of patients receiving chemotherapy. TRAEs led to death in two patients receiving Keytruda plus chemotherapy and one patient receiving chemotherapy.

During the adjuvant phase , TRAEs of any grade occurred in 48.1% of patients receiving Keytruda (n=547) and 43.0% of patients receiving placebo (n=314). Grade 3-5 TRAEs occurred in 5.7% of patients receiving Keytruda monotherapy and 1.9% of patients receiving placebo. There were no TRAEs occurring in ?10% of patients. TRAEs resulting in discontinuation of treatment occurred in 3.3% of patients receiving Keytruda monotherapy and 1.3% of patients receiving placebo. TRAEs led to death in one patient receiving Keytruda monotherapy. Immune-mediated adverse events and infusion reactions of any grade in the combined neoadjuvant and adjuvant phases occurred in 42.3% of patients receiving the Keytruda regimen and 21.3% of patients receiving the chemotherapy-placebo regimen. The most common of these events (occurring in greater than 10% of patients) were infusion reactions (17.7%) and hypothyroidism (14.9%) in the Keytruda regimen and infusion reactions (11.6%) in the chemotherapy-placebo regimen. Immune-mediated adverse events led to death in one patient in the Keytruda regimen.