Keytruda Plus Chemotherapy Significantly Reduces Recurrence Risk in High-Risk Early-Stage Triple-Negative Breast Cancer, Phase 3 Results Published in NEJM

On February 10, 2022, MSD announced that the results of the Phase 3 clinical trial of its重磅 anti-PD-1 antibody therapy Keytruda for the treatment of high-risk early-stage triple-negative breast cancer (TNBC) were published in the prestigious medical journal *The New England Journal of Medicine*. The trial results showed that compared with the chemotherapy + placebo group, using Keytruda in combination with chemotherapy as neoadjuvant treatment before surgery, followed by Keytruda monotherapy as adjuvant treatment after surgery, significantly prolonged the event-free survival (EFS) of patients with high-risk early-stage TNBC. In July last year, the U.S. FDA approved Keytruda for use in combination with chemotherapy as a neoadjuvant therapy before surgery and as a monotherapy adjuvant treatment after surgery for patients with high-risk early-stage TNBC, becoming the first immunotherapy regimen approved for this population.

TNBC is an aggressive type of breast cancer that occurs in 10-15% of breast cancer patients, with a higher risk of disease recurrence within the first five years after diagnosis. Due to the lack of expression of estrogen receptor (ER), progesterone receptor (PR), or human epidermal growth factor receptor 2 (HER2), patients are unable to receive targeted therapies aimed at these receptors, resulting in limited treatment options.

Keytruda works by enhancing the body's immune system to help monitor and combat tumor cells. As a humanized monoclonal antibody, it blocks the interaction between PD-1 and its ligands PD-L1 and PD-L2, thereby activating T lymphocytes. Merck Sharp & Dohme AG currently has over 1700 trials investigating the efficacy and safety of Keytruda across various cancers and treatment settings.

The trial met the primary endpoint of pathological complete response (pCR) at the first interim analysis: pCR was observed in 64.8% of patients (n=260/401) in the Keytruda + chemotherapy group, an increase of 13.6% compared to 51.2% in the chemotherapy + placebo group (n=103/201) (p=0.00055). After a median follow-up of 39 months, the trial reached another primary endpoint, EFS, with Keytruda reducing the risk of events or death by 37% compared to the control group (HR=0.63 [95% CI, 0.48-0.82]; p<0.001). A total of 15.7% (n=123/784) of patients treated with the Keytruda regimen experienced EFS events, compared to 23.8% (n=93/390) in the control group. The estimated 3-year EFS rate in the Keytruda group was 84.5% (95% CI, 81.7-86.9), while it was 76.8% (95% CI, 72.2-80.7) in the control group.

Image source: Reference [2]

The trial also evaluated the key secondary endpoint, overall survival (OS). Although the OS data did not reach statistical significance, the risk of death was reduced by 28% in the Keytruda group compared to the chemotherapy + placebo group (HR=0.72 [95% CI, 0.51-1.02]). In terms of safety, the safety profile of the Keytruda regimen was consistent with the known profiles of each regimen, and no new safety issues were identified.

References:

[1] 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. Retrieved February 10， 2022, from https://www.merck.com/news/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/

[2] Schmid et al., (2022). Event-free Survival with Pembrolizumab in Early Triple-Negative Breast Cancer. NEJM, DOI: 10.1056/NEJMoa2112651

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