Merck's Keytruda Achieves Phase 3 Primary Endpoint, Reducing Risk of Disease Progression by 37% in High-Risk Early-Stage Triple-Negative Breast Cancer

Today, MSD announced that Keytruda, its blockbuster anti-PD-1 therapy, has achieved positive results in a pivotal Phase 3 clinical trial for the treatment of high-risk early-stage triple-negative breast cancer (TNBC). In this trial, Keytruda was administered in combination with chemotherapy as neoadjuvant therapy and subsequently as adjuvant monotherapy following surgical resection. Compared with adjuvant placebo following neoadjuvant chemotherapy, this regimen significantly improved patients' event-free survival (EFS). The press release noted that this marks the first time an anti-PD-1/PD-L1 therapy has demonstrated a statistically significant EFS benefit in these patients when used as combined neoadjuvant and adjuvant therapy.

The trial results showed that at a median follow-up of 39 months, compared with the chemotherapy plus placebo regimen, treatment with Keytruda reduced the risk of an EFS event by 37% (HR=0.63, 95% CI, 0.48–0.82; p=0.00031), which was statistically and clinically significant. EFS was defined as the time from randomization to the first occurrence of disease progression precluding surgery, local or distant recurrence, second primary malignancy, or death from any cause.

Previously, KEYNOTE-522 met its primary endpoint of pathological complete response (pCR) at the first interim analysis. The trial will continue for further evaluation of overall survival (OS). At the fourth interim analysis, compared with the chemotherapy-placebo regimen, patients receiving the Keytruda regimen demonstrated a 28% reduction in the risk of death (HR=0.72, 95% CI, 0.51–1.02; p=0.03214). This difference has not yet reached statistical significance. The safety profile of the Keytruda regimen was consistent with the known profiles of each regimen, and no new safety signals were identified.

Patients with triple-negative breast cancer (TNBC) account for 15–20% of all breast cancer cases and are more prevalent in women under the age of 40. Due to the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), these patients are ineligible for targeted therapies directed at these receptors, resulting in limited treatment options. TNBC is one of the most aggressive subtypes of breast cancer, characterized by high invasiveness, a strong propensity for metastasis, and a very poor prognosis. The median survival time after diagnosis typically does not exceed 20 months, with a 5-year survival rate of less than 15%.

Keytruda is an anti-PD-1 therapy that enhances the immune system's ability to recognize and combat tumor cells by blocking PD-1-mediated immunosuppressive signals. Since its market launch, this drug has received FDA approval for more than 30 indications, including melanoma and non-small cell lung cancer.

Note: The original text has been abridged.

References:

[1] KEYTRUDA^® (pembrolizumab) Plus Chemotherapy Before Surgery and Continued as a Single Agent After Surgery Showed Statistically Significant Event-Free Survival (EFS) Result Versus Neoadjuvant Chemotherapy Alone in High-Risk Early-Stage TNBC. Retrieved July 15, 2021, from https://www.businesswire.com/news/home/20210715005674/en

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