KEYNOTE-522 Trial Results Show Neoadjuvant Keytruda Plus Chemo Improves Overall Survival in Triple-Negative Breast Cancer

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A pre-specified interim analysis of the Phase III KEYNOTE-522 trial (NCT03036488) found that Keytruda (pembrolizumab; Merck) plus chemotherapy administered as neoadjuvant treatment and then as monotherapy postsurgery achieved the key secondary endpoint of overall survival (OS) in patients with high-risk early-stage triple-negative breast cancer (TNBC). An independent Data Monitoring Committee found that the therapy demonstrated a statistically significant and clinically meaningful OS improvement vs. pre-operative chemotherapy in the trial.¹

“This is a significant milestone, as it is the first time an immunotherapy-based regimen has demonstrated a statistically significant overall survival benefit compared to chemotherapy alone in patients with high-risk early-stage triple-negative breast cancer,” Gursel Aktan, MD, PhD, vice president, global clinical development, Merck Research Laboratories, said in a press release. “To have achieved overall survival from this landmark study is highly encouraging and builds upon the positive pathological complete response and event-free survival results that led to approvals for this regimen around the world.”¹

Keytruda is an anti-PD-1 therapy that improves the immune system's ability to detect and fight tumor cells. The humanized monoclonal antibody blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, which leads to the activation of T lymphocytes that could affect the tumor and healthy cells.

Keytruda has been approved by the FDA for two indications in TNBC. The agent has been approved for patients with high-risk early-stage TNBC combined with chemotherapy as neoadjuvant treatment followed by treatment as a single agent postsurgery; and combined with chemotherapy for patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.

To date, more than 1600 trials are evaluating Keytruda across a range of cancer types and treatment settings. Keytruda also has approved indications in melanoma; non-small cell lung cancer; head and neck squamous cell cancer; classical Hodgkin lymphoma; primary mediastinal large B-cell lymphoma; urothelial carcinoma; gastric cancer; microsatellite instability-high or mismatch repair deficient cancer; microsatellite instability-high or mismatch repair deficient colorectal cancer; esophageal cancer; cervical cancer; hepatocellular carcinoma; Merkel cell carcinoma; renal cell carcinoma; endometrial carcinoma; tumor mutational burden-high cancer; cutaneous squamous cell carcinoma; and triple-negative breast cancer.²

KEYNOTE 522 is the fourth trial involving a Keytruda-based regimen to show an OS benefit for an earlier stage of cancer, following KEYNOTE-A18 for cervical cancer, KEYNOTE-671 for non-small cell lung cancer, and KEYNOTE-564 for renal cell carcinoma.

The randomized, double-blind KEYNOTE 522 trial enrolled 1174 patients, who were randomly assigned on a 2:1 basis to receive either Keytruda plus chemotherapy consisting of paclitaxel and carboplatin followed by Keytruda plus chemotherapy consisting of cyclophosphamide and either doxorubicin or epirubicin as neoadjuvant treatment followed by adjuvant single-agent Keytruda (n=784); or placebo plus chemotherapy consisting of paclitaxel and carboplatin, followed by placebo plus chemotherapy consisting of cyclophosphamide and either doxorubicin or epirubicin as neoadjuvant therapy followed by placebo monotherapy as adjuvant therapy (n=390).

The trial’s dual primary endpoints were pathological complete response rate, defined as pathological stage ypT0/Tis ypN0 at the time of definitive surgery; and event-free survival that is defined as the time from randomization to the time of first occurrence of either disease progression that precluded definitive surgery, a local/distant recurrence, a secondary primary cancer, or death from any cause.

In addition to achieving the OS secondary endpoint, the safety profile of Keytruda was consistent with what has previously been reported in clinical trials, with no new safety signals. The findings from the trial will be presented at an upcoming medical meeting and shared with regulatory authorities, according to Merck.

References

1. Merck Announces Phase 3 KEYNOTE-522 Trial Met its Overall Survival (OS) Endpoint in Patients With High-Risk Early-Stage Triple Negative Breast Cancer (TNBC). News release. Merck. May 28, 2024. Accessed May 28, 2024. https://www.merck.com/news/merck-announces-phase-3-keynote-522-trial-met-its-overall-survival-os-endpoint-in-patients-with-high-risk-early-stage-triple-negative-breast-cancer-tnbc/

2. Merck Announces Phase 3 KEYNOTE-811 Trial Met Dual Primary Endpoint of Overall Survival (OS) as First-Line Treatment in Patients With HER2-Positive Advanced Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma. News release. Merck. May 1, 2024. Accessed May 28, 2024. https://www.merck.com/news/merck-announces-phase-3-keynote-811-trial-met-dual-primary-endpoint-of-overall-survival-os-as-first-line-treatment-in-patients-with-her2-positive-advanced-gastric-or-gastroesophageal-junction-gej/