Keytruda (pembrolizumab) is a programmed death receptor-1 (PD-1)-blocking antibody.
Keytruda is specifically indicated as monotherapy for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.
Keytruda is supplied as a solution for intravenous infusion. The recommended dose of Keytruda in patients with locally advanced or metastatic urothelial carcinoma is 200 mgadministered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression. The recommended dose of Keytruda in patients with high-risk BCG-unresponsive non-muscle invasive bladder cancer is 200 mgadministered as an intravenous infusion over 30 minutes every 3 weeks until persistent or recurrent high-risk NMIBC, disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.
The FDA approval of Keytruda for bladder cancer was based on data from KEYNOTE-057, a multicenter, open-label, single-arm trial in 96 patients with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. In this study, BCG-unresponsive high-risk NMIBC was defined as persistent disease despite adequate BCG therapy, disease recurrence after an initial tumor-free state following adequate BCG therapy, or T1 disease following a single induction course of BCG. Adequate BCG therapy was defined as administration of at least five of six doses of an initial induction course plus either of: at least two of three doses of maintenance therapy or at least two of six doses of a second induction course. Prior to treatment, all patients had undergone transurethral resection of bladder tumor (TURBT) to remove all resectable disease (Ta and T1 components). Residual CIS (Tis components) not amenable to complete resection was allowed. The trial excluded patients with muscle invasive (i.e., T2, T3, T4) locally advanced non-resectable or metastatic urothelial carcinoma, concurrent extra-vesical (i.e., urethra, ureter or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium, or autoimmune disease or a medical condition that required immunosuppression.
Patients received Keytruda 200 mg every three weeks until unacceptable toxicity, persistent or recurrent high-risk NMIBC, or progressive disease. Assessment of tumor status was performed every 12 weeks for two years and then every 24 weeks for three years, and patients without disease progression could be treated for up to 24 months. The major efficacy outcome measures were complete response (as defined by negative results for cystoscopy [with TURBT/biopsies as applicable], urine cytology, and computed tomography urography [CTU] imaging) and duration of response.
The median follow-up time was 28.0 months (range: 4.6 to 40.5 months). Keytruda demonstrated a complete response rate of 41%. Among the 39 patients who achieved a complete response, the median duration of response was 16.2 months, and 46% had a response of 12 months or longer.
Adverse effects associated with Keytruda for bladder cancer may include, but are not limited to, the following:
Keytruda (Pembrolizumab) is a programmed death receptor-1 (PD 1)-blocking antibody. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.
For additional information regarding Keytruda or bladder cancer, please visit the Keytruda web page.