KEYNOTE-522 Shows Prolonged EFS With Adjuvant Pembrolizumab in High-Risk, Early-Stage TNBC

Treatment with adjuvant pembrolizumab following neoadjuvant pembrolizumab (Keytruda) plus chemotherapy showed a statistically significant prolonged event-free survival (EFS) in patients with high-risk early-stage triple-negative breast cancer (TNBC), according to results from the phase 3 KEYNOTE-522 announced by Merck and published in the New England Journal of Medicine.

In 2021, the FDA approved pembrolizumab based on results of the randomized, double-blind, KEYNOTE-522 trial, which is the first immunotherapy for this indication, plus chemotherapy as neoadjuvant treatment for patients with early-stage TNBC. The drug is given into the bloodstream, with the number of sessions depending on the type of cancer.

Results from the primary EFS analysis found that out of the 784 patients treated with the experimental regimen, EFS events occurred in 15.7% of patients compared to 23.8% among 390 in the placebo plus chemotherapy followed by placebo arm (HR, 0.63; 95% CI, 0.48-0.82; P = .00031).

At a median follow-up of 39 months, pembrolizumab produced an improved EFS compared with chemotherapy alone with patients in the PD-L1–positive group having a 33% reduced risk of EFS events with pembrolizumab when compared with the placebo group (HR, 0.67; 95% CI, 0.49-0.92). Patients in the PD-L1–negative group who received the pembrolizumab regimen had a reduced risk for EFS events by 52% when compared to the placebo-chemotherapy group (HR, 0.48; 95% CI, 0.28-0.85). The 36-month EFS rates were 84.5% versus 76.8%, respectively.

“These data, which supported the FDA approval and updates to the NCCN guidelines, establish that Keytruda plus chemotherapy as neoadjuvant therapy followed by adjuvant Keytruda could change clinical practice for the treatment of patients with high-risk early-stage TNBC,” said Dr. Peter Schmid, lead, center for experimental cancer medicine, Barts Cancer Institute in London, England. “KEYNOTE-522 is the first prospective randomized phase 3 trial to show an improvement in event-free survival among patients with stage II and stage III TNBC.”

Primary end points of the trial consist of pathological complete response (pCR), and EFS. Some secondary end points include pCR rate using alternative definitions, overall survival (OS) in all patients randomized, pCR rate according to all definitions, EFS and OS in patients whose tumors express PD-L1 (Combined Positive Score ≥1), safety and health-related quality of life assessments.

The safety profile of the pembrolizumab plus chemotherapy regimen was consistent with prior profiles, and no new safety concerns were identified. Additional detailed efficacy and safety data are also featured in the publication.

“The study of Keytruda in earlier disease states has long been a critical aspect of our clinical program,” Roy Baynes, MBBCh, MMed, PhD, FCP, FACP, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We are incredibly proud that the New England Journal of Medicine has chosen to publish data from this pivotal neoadjuvant/adjuvant trial of Keytruda in high-risk early-stage TNBC for the second time. Results from KEYNOTE-522, in which the Keytruda regimen showed a significant 37% reduction in the risk of EFS events compared to neoadjuvant chemotherapy, represent an important advance and support earlier intervention with Keytruda in these patients.”

Additionally, immune-mediated adverse events (AEs) of any grade occurred in 33.5% of patients receiving pembrolizumab plus chemotherapy and 11.3% of patients receiving the chemotherapy-placebo regimen. Endocrine disorders were observed to be more common with the pembrolizumab plus chemotherapy regimen as compared to the chemotherapy-placebo regimen.

Immune-mediated AEs led to death in 0.3% of patients receiving the pembrolizumab plus chemotherapy regimen (n = 2) compared to no patients receiving the chemotherapy-placebo regimen. Most immune-mediated AEs occurred during the neoadjuvant phase rather than the adjuvant phase.

^REFERENCES:

^{Pivotal phase 3 Data for KEYTRUDA® (pembrolizumab) in High-Risk Early-Stage Triple-Negative Breast Cancer (TNBC) Published in the New England Journal of Medicine. News Release. Merck; February 09, 2022. Accessed February 10, 2022. https://bit.ly/3sqSQbk}