Merck Announces KEYNOTE-522 Phase 3 Trial Results Showing Event-Free Survival Benefit of Pembrolizumab in High-Risk Early-Stage Triple-Negative Breast Cancer

SHANGHAI, Aug. 3, 2021 /PRNewswire/ -- MSD (MSD is the corporate brand name of Merck & Co., Inc., Kenilworth, New Jersey, USA) announced event-free survival (EFS) data from the pivotal phase 3 neoadjuvant/adjuvant KEYNOTE-522 trial. EFS is defined as the time from randomization to the first occurrence of disease progression precluding definitive surgery, local or distant recurrence, a second primary malignancy, or death from any cause. The KEYNOTE-522 study was designed to evaluate the efficacy of pembrolizumab, an MSD PD-1 inhibitor, in combination with chemotherapy as neoadjuvant treatment, followed by pembrolizumab monotherapy as adjuvant treatment, versus chemotherapy as neoadjuvant treatment followed by placebo as adjuvant treatment in patients with high-risk early-stage triple-negative breast cancer (TNBC). The results of the KEYNOTE-522 trial were presented on July 16 during the European Society for Medical Oncology (ESMO) Virtual Plenary.

According to data from the World Health Organization, in 2020, there were approximately 416,000 new cases of breast cancer in China, ranking first in incidence among female cancers, with approximately 117,000 deaths.^[1]。TNBC is currently the most challenging type in breast cancer treatment, referring to a breast cancer subtype characterized by negative expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).^[2]，Accounts for approximately 17% of all breast cancers^[3]。Early local recurrence and a high propensity for distant metastasis are key factors contributing to treatment failure and mortality in TNBC.

“Given that patients with high-risk early-stage TNBC are prone to recurrence within five years of diagnosis, they urgently need new treatment options,” said Dr. Peter Schmid, Head of the Experimental Cancer Medicine Centre at Barts Cancer Institute in London, UK. “KEYNOTE-522 aims to evaluate whether the regimen of pembrolizumab plus chemotherapy as neoadjuvant therapy, followed by pembrolizumab monotherapy as adjuvant therapy, can benefit patients with early-stage cancer. With over three years of follow-up to date, we hope to provide new treatment options for these female patients.”

“The KEYNOTE-522 study is the first large, randomized phase III clinical trial to report EFS results in patients with stage II and III TNBC,” said Dr. Vicki Goodman, Vice President of Clinical Research at MSD. “We are excited about the potential of pembrolizumab for these patients.”

To date, the indications for pembrolizumab approved by the National Medical Products Administration (NMPA) of China are: indicated for the treatment of unresectable or metastatic melanoma after failure of first-line therapy; indicated for patients assessed with a PD-L1 Tumor Proportion Score (TPS) by a test approved by the National Medical Products Administration>=For first-line monotherapy treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) gene mutation-negative and anaplastic lymphoma kinase (ALK)-negative status, 1%; in combination with pemetrexed and platinum-based chemotherapy for the first-line treatment of metastatic non-squamous non-small cell lung cancer (NSCLC) with EGFR gene mutation-negative and ALK-negative status; in combination with carboplatin and paclitaxel for the first-line treatment of patients with metastatic squamous non-small cell lung cancer (NSCLC); as monotherapy for tumors expressing PD-L1 (Combined Positive Score [CPS]) as assessed by a validated test>=10) for the treatment of patients with locally advanced or metastatic esophageal squamous cell carcinoma (ESCC) who have failed prior first-line systemic therapy; as a monotherapy for patients whose tumors express PD-L1 (Combined Positive Score (CPS)) as assessed by a fully validated test (>=20) first-line treatment for patients with metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC); and as monotherapy for the first-line treatment of patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC) whose KRAS, NRAS, and BRAF genes are wild-type. The indication for pembrolizumab in combination with chemotherapy for neoadjuvant treatment and subsequently as monotherapy for adjuvant treatment in patients with high-risk early-stage triple-negative breast cancer (TNBC) has not yet been approved by the NMPA.

[1]IARC. China Fact Sheet (2020).

[2] Sun Xiaomeng, Gao Shegan. Current Status and New Advances in Clinical Treatment of Triple-Negative Breast Cancer[J]. Practical Journal of Cancer, 2020, v.35; No.219(06): 171-173.

[3]Nancy Lin, Ann Vanderplas, Melissa Hughes, et al. Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network[J]. Cancer, 2012, 118(22):5463-5472.