Try our mobile app
Late-breaking results selected for presentation during a Presidential Symposium session and an official Press Briefing at the European Society for Medical Oncology Congress 2024 and simultaneous publication in the New England Journal of Medicine
KEYTRUDA is the first and only immunotherapy-based regimen to show a statistically significant and clinically meaningful improvement in overall survival as pre-operative (neoadjuvant) treatment with chemotherapy and then as a single agent after surgery (adjuvant) compared to pre-operative chemotherapy in patients with high-risk early-stage TNBC
KEYNOTE-522 marks the fourth study of a KEYTRUDA-based regimen in an earlier stage of cancer to demonstrate an OS benefit
RAHWAY, N.J.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, today announced the first-time presentation of overall survival (OS) results from the Phase 3 KEYNOTE-522 trial evaluating KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in combination with chemotherapy as pre-operative (neoadjuvant) treatment and then continuing as a single agent after surgery (adjuvant) for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC). After a median follow-up of 75.1 months (range, 65.9-84.0), the KEYTRUDA regimen significantly improved OS, a key secondary endpoint, reducing the risk of death by 34% (HR=0.66 [95% CI, 0.50-0.87]; p=0.0015) in patients with high-risk early-stage TNBC compared to the chemotherapy-placebo regimen (placebo plus chemotherapy followed by placebo after surgery). The five-year OS rate was 86.6% (95% CI, 84.0-88.8) for patients who received the KEYTRUDA regimen versus 81.7% (95% CI, 77.5-85.2) for patients who received the chemotherapy-placebo regimen. Median OS was not reached in either group. The safety profile of KEYTRUDA was consistent with that observed in previously reported studies with no new safety signals observed.
These late-breaking data are being presented for the first time today during a Presidential Symposium session at the European Society for Medical Oncology (ESMO) Congress 2024 (presentation #LBA4) and were selected for an official Press Briefing. These data are also being simultaneously published in the New England Journal of Medicine. KEYTRUDA is the first and only immunotherapy-based regimen to show a statistically significant and clinically meaningful improvement in OS as neoadjuvant treatment with chemotherapy and then continued as a single agent as adjuvant treatment compared to placebo plus chemotherapy followed by placebo after surgery in patients with high-risk early-stage TNBC.
In pre-specified exploratory subgroup analyses of OS, the benefit of the KEYTRUDA regimen was consistent across pre-specified subgroups, including those defined by PD-L1 expression, tumor size and nodal status.
“These impactful overall survival results add to the previously reported pathological complete response and event-free survival data from the KEYNOTE-522 trial,” said Dr. Peter Schmid, lead, Centre for Experimental Cancer Medicine, Barts Cancer Institute in London, England. “In this study, pembrolizumab plus chemotherapy as neoadjuvant treatment and continued as a single agent after surgery reduced the risk of death by more than one-third compared to neoadjuvant chemotherapy, reinforcing the important role this regimen plays in the treatment of high-risk early-stage triple-negative breast cancer.”
“KEYTRUDA is the first and only immunotherapy-based regimen to show a statistically significant and clinically meaningful improvement in overall survival compared to chemotherapy alone in patients with high-risk early-stage triple-negative breast cancer,” said Dr. Gursel Aktan, vice president, global clinical development, Merck Research Laboratories. “This is an important milestone and represents the fourth KEYTRUDA study to demonstrate a significant overall survival benefit in an earlier stage of cancer, highlighting our efforts to help extend the lives of patients with certain cancers across different stages of disease.”
KEYNOTE-522 is one of four Phase 3 studies of a KEYTRUDA-based regimen in an earlier stage of cancer to demonstrate an OS benefit, including KEYNOTE-A18 in newly diagnosed, high-risk locally advanced cervical cancer (as treatment with chemoradiotherapy, compared to chemoradiotherapy), KEYNOTE-671 in resectable stage II, IIIA or IIIB non-small cell lung cancer (as treatment with chemotherapy before surgery and then as a single agent after surgery, compared to pre-operative chemotherapy) and KEYNOTE-564 in renal cell carcinoma for patients at intermediate-high or high risk of recurrence following nephrectomy, or following nephrectomy and resection of metastatic lesions (compared to placebo).
As previously announced, the KEYNOTE-522 trial met its dual primary endpoints of pCR and event-free survival (EFS) at earlier interim analyses. Based on these results, KEYTRUDA is approved in the U.S. in combination with chemotherapy as neoadjuvant treatment and then continued as a single agent as adjuvant treatment after surgery for the treatment of patients with high-risk early-stage TNBC. KEYNOTE-522 also supported regulatory approvals for certain patients with TNBC in Europe, Japan and other countries globally.
As announced, data spanning more than 20 types of cancer are being presented from Merck’s broad oncology portfolio and investigational pipeline at the ESMO Congress 2024.
Study design and additional data from KEYNOTE-522
KEYNOTE-522 is a Phase 3, randomized, double-blind trial (ClinicalTrials.gov, NCT03036488) evaluating KEYTRUDA in combination with chemotherapy as pre-operative (neoadjuvant) treatment and then continuing as a single agent after surgery (adjuvant) compared to placebo plus chemotherapy as neoadjuvant treatment followed by placebo as adjuvant treatment in patients with high-risk early-stage TNBC (stage T1c N1-2 or T2-4 N0-2 per AJCC). The dual primary endpoints were pCR rate, defined as pathological stage ypT0/Tis ypN0 at the time of definitive surgery, and EFS, 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 second primary cancer or death from any cause. A key secondary endpoint was OS. The study enrolled 1,174 patients who were randomized 2:1 to receive either:
After a median follow-up of 75.1 months (range, 65.9-84.0), the KEYTRUDA regimen reduced the risk of EFS events by 35% (HR=0.65 [95% CI, 0.51-0.83]) in patients with high-risk early-stage TNBC compared to the chemotherapy-placebo regimen. The five-year EFS rate was 81.2% (95% CI, 78.3-83.8) for those treated with the KEYTRUDA regimen compared to 72.2% (95% CI, 67.4-76.4) for those treated with the chemotherapy-placebo regimen.
At this analysis, treatment-related adverse events (TRAEs) were examined in the neoadjuvant phase, the adjuvant phase and the combined phases. TRAEs in the neoadjuvant phase have been previously reported. At the time of this data cutoff, no patients were still receiving protocol treatment. For the combined neoadjuvant and adjuvant phases, TRAEs occurred in 98.9% of patients receiving the KEYTRUDA regimen (n=783) and 99.7% of patients receiving the chemotherapy-placebo regimen (n=389); Grade 3-5 TRAEs occurred in 82.4% versus 78.7%, respectively. TRAEs led to death in 0.5% of patients receiving the KEYTRUDA regimen (n=4) and 0.3% of patients receiving the chemotherapy-placebo regimen (n=1). No new safety concerns were identified.
Immune-mediated adverse events (AEs) and infusion reactions of any grade in the combined neoadjuvant and adjuvant phases occurred in 44.8% of patients receiving the KEYTRUDA regimen and 22.9% of patients receiving the chemotherapy-placebo regimen. The most common of these events (occurring in ≥10% of patients) were infusion reactions (18.0%) and hypothyroidism (15.1%) in patients receiving the KEYTRUDA regimen and infusion reactions (11.6%) in patients receiving the chemotherapy-placebo regimen. Immune-mediated AEs led to death in 0.3% of patients receiving the KEYTRUDA regimen (n=2) and no patients receiving the chemotherapy-placebo regimen.
About triple-negative breast cancer (TNBC)
Triple-negative breast cancer is the most aggressive type of breast cancer, which has the highest risk of recurrence within the first five years after diagnosis and is associated with worse outcomes compared to other forms of breast cancer. Approximately 10-15% of patients with breast cancer are diagnosed with TNBC. While some breast cancers may test positive for estrogen receptors, progesterone receptors or overexpression of human epidermal growth factor receptor 2 (HER2), TNBC tests negative for all three. Triple-negative breast cancer tends to be more common in people who are younger than 40 years of age, who are Black or who have a BRCA1 mutation.
About Merck’s research in women’s cancers
Merck is advancing research aimed at expanding treatment options for certain breast and gynecologic (ovarian, cervical and endometrial) cancers, with a goal of improving outcomes for more patients affected by these diseases. Breast cancer and gynecological cancers are the first and second most commonly occurring cancer types among women worldwide, respectively, and Merck aims to give patients facing these devastating diseases options. With more than 20 clinical trials in more than 18,000 patients around the world, Merck is driving innovative research to purposefully advance standards of care in women’s cancers. Merck’s research efforts include trials focused on evaluating its medicines in earlier stages, as well as identifying novel mechanisms and new combinations with these treatments. Merck is working to develop a portfolio and pipeline to address the impact of women’s cancers on patients, their families and communities globally.
About Merck’s early-stage cancer clinical program
Finding cancer at an earlier stage may give patients a greater chance of long-term survival. Many cancers are considered most treatable and potentially curable in their earliest stage of disease. Building on the strong understanding of the role of KEYTRUDA in later-stage cancers, Merck is evaluating our portfolio of medicines and pipeline candidates in earlier disease states, with more than 30 ongoing registrational studies across multiple types of cancer.
About KEYTRUDA® (pembrolizumab) injection, 100 mg
KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.
Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.
Triple-Negative Breast Cancer
KEYTRUDA is indicated for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy as neoadjuvant treatment, and then continued as a single agent as adjuvant treatment after surgery.
KEYTRUDA, in combination with chemotherapy, is indicated for the treatment of patients with locally recurrent unresectable or metastatic TNBC whose tumors express PD-L1 (CPS ≥10) as determined by an FDA-approved test.
See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.
Selected Important Safety Information for KEYTRUDA
Severe and Fatal Immune-Mediated Adverse Reactions
KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or the programmed death ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.
Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.
Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.
Immune-Mediated Pneumonitis
KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.
Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.
Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.
Immune-Mediated Colitis
KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (
The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.
