What is the use of Keytruda (pembrolizumab)?

From the Guidelines

Keytruda (pembrolizumab) is a recommended treatment option for patients with unresectable or metastatic MSI-H or dMMR solid tumors, including certain types of breast, prostate, and bladder cancer, who have progressed on prior treatment and have no satisfactory alternative treatment options, as supported by the most recent evidence from 2023 1. The standard adult dose of Keytruda is 200 mg intravenously once every 3 weeks or 400 mg every 6 weeks. Keytruda works by blocking a protein called PD-1 on T cells, which helps these immune cells recognize and attack cancer cells more effectively. Common side effects include fatigue, rash, diarrhea, and nausea, while more serious immune-related adverse effects can affect the lungs, liver, kidneys, or endocrine system. Patients receiving Keytruda should report any new or worsening symptoms to their healthcare provider immediately, as early management of side effects is crucial. Regular monitoring through blood tests and imaging studies is necessary throughout treatment to assess response and detect potential complications. The most recent study from 2023 1 provides the highest quality evidence for the use of Keytruda in patients with MSI-H or dMMR metastatic castration-resistant prostate cancer (mCRPC) whose disease has progressed through docetaxel and a novel hormone therapy. The prevalence of MMR deficiency in metastatic CPRC is estimated at 2%–5%, and testing for MSI-H or dMMR can be performed using DNA testing or immunohistochemistry. If tumor MSI-H or dMMR is identified, referral to genetic counseling for consideration of germline testing for Lynch syndrome is recommended. Keytruda has shown durable responses in patients with MSI-H or dMMR solid tumors, with response durations of ≥ 12 months observed in an estimated 86.9% of patients, and response durations of ≥ 24 months observed in an estimated 77.6% of patients, as reported in the KEYNOTE-158 study 1. Overall, Keytruda is a valuable treatment option for patients with certain types of cancer, including breast, prostate, and bladder cancer, and its use should be considered in the context of individual patient needs and tumor characteristics. Some of the key benefits of Keytruda include its ability to induce durable responses, its relatively favorable safety profile, and its potential to improve overall survival in certain patient populations. However, Keytruda is not without risks, and patients should be closely monitored for potential side effects and immune-related adverse effects. In addition to its use in breast, prostate, and bladder cancer, Keytruda has also been studied in other types of cancer, including melanoma, lung cancer, and head and neck cancer, and has shown promising results in these settings as well. Further research is needed to fully understand the benefits and risks of Keytruda and to determine its optimal use in different patient populations. Keytruda has been associated with immune-mediated side effects, which include colitis, hepatitis, endocrinopathies, pneumonitis, or nephritis, and patients should be closely monitored for these potential complications. The use of Keytruda in combination with other therapies, such as chemotherapy or targeted therapy, is also being explored, and may offer additional benefits for certain patient populations. In summary, Keytruda is a valuable treatment option for patients with certain types of cancer, including breast, prostate, and bladder cancer, and its use should be considered in the context of individual patient needs and tumor characteristics, as supported by the most recent evidence from 2023 1.

From the FDA Drug Label

KEYTRUDA is a prescription medicine used to treat: a kind of skin cancer called melanoma a kind of lung cancer called non-small cell lung cancer (NSCLC) a kind of cancer in adults called malignant pleural mesothelioma (MPM) that affects the lining of the lungs and chest wall. a kind of cancer called head and neck squamous cell cancer (HNSCC) a kind of cancer called classical Hodgkin lymphoma (cHL): a kind of cancer that is shown by a test to be tumor mutational burden-high (TMB-H) a kind of skin cancer called cutaneous squamous cell carcinoma (cSCC). a kind of cancer called triple-negative breast cancer (TNBC) a kind of liver cancer called hepatocellular carcinoma (HCC) a kind of bile duct or gallbladder cancer called biliary tract cancer (BTC). a kind of skin cancer called Merkel cell carcinoma (MCC) in adults and children. a kind of kidney cancer called renal cell carcinoma (RCC). a kind of uterine cancer called advanced endometrial carcinoma

Keytruda is a prescription medicine used to treat various types of cancer, including:

• Melanoma
• Non-small cell lung cancer (NSCLC)
• Malignant pleural mesothelioma (MPM)
• Head and neck squamous cell cancer (HNSCC)
• Classical Hodgkin lymphoma (cHL)
• Tumor mutational burden-high (TMB-H)
• Cutaneous squamous cell carcinoma (cSCC)
• Triple-negative breast cancer (TNBC)
• Hepatocellular carcinoma (HCC)
• Biliary tract cancer (BTC)
• Merkel cell carcinoma (MCC)
• Renal cell carcinoma (RCC)
• Advanced endometrial carcinoma 2, 2, 2

From the Research

Keytruda (Pembrolizumab) Overview

• Keytruda, also known as pembrolizumab, is a humanized monoclonal antibody that targets the PD-1 receptor, helping to restore the body's immune response against cancer cells 3.
• It has been approved for the treatment of various types of cancer, including melanoma, non-small cell lung cancer, head and neck squamous cell carcinoma, colorectal cancer, urothelial cancer, and Hodgkin lymphoma.

Efficacy and Safety

• Studies have shown that pembrolizumab is effective in treating patients with advanced tumors, with a low incidence of treatment-emergent antidrug antibodies (ADAs) 3.
• The presence of pembrolizumab-specific ADAs did not impact pembrolizumab exposure, nor did pembrolizumab immunogenicity affect the incidence of drug-related adverse events (AEs) or infusion-related reactions 3.
• A randomized phase 2 trial found that pembrolizumab alone or in combination with low-dose chemotherapy was effective in treating patients with non-small cell lung cancer and poor performance status, with better long-term survival compared to historical outcomes of platinum-based chemotherapy 4.

Tumor Mutational Burden

• A study found that pembrolizumab demonstrated antitumor activity in patients with tumors with high tumor mutational burden (HTMB), with a disease control rate of 31% in patients with colorectal cancer and 45% in patients with other advanced cancers 5.
• The study suggested that pembrolizumab may be a promising treatment option for patients with HTMB tumors.

Immunotherapy in Cancer Management

• A literature review found that immunotherapy, including pembrolizumab, is a promising alternative for the treatment of non-small cell lung cancer, with benefits overcoming risks compared to other therapies 6.
• The review highlighted the importance of immunotherapy in cancer treatment, particularly in oral cancers, where the complex tumor microenvironment promotes tumor growth and inhibits immune responses 7.

Microenvironment-Based Immunotherapy

• A comprehensive review discussed the effectiveness of immunotherapy in oral cancer, including the use of pembrolizumab, which targets immune checkpoints such as PD-1 and CTLA-4 inhibitors 7.
• The review explored how the tumor microenvironment controls tumor proliferation and metastasis via autocrine-paracrine signaling pathways and highlighted the potential of immunotherapy to regulate tumor growth and promote tumor destruction.