Pembrolizumab

Pembrolizumab is a humanised monoclonal antibody and immune checkpoint inhibitor used in the treatment of several types of cancer. It belongs to the programmed death receptor-1 (PD-1) blocking class of medicines. PD-1 is a protein found on T cells, which are immune cells involved in recognising and attacking abnormal cells. Some cancer cells use the PD-1 pathway to reduce immune activity and evade destruction. Pembrolizumab binds to PD-1 and blocks its interaction with its ligands, PD-L1 and PD-L2, helping restore antitumour immune responses. Its effectiveness depends on factors such as cancer type, disease stage, tumour biology and previous treatment.

Pembrolizumab is used alone or in combination with chemotherapy, targeted medicines or other anticancer treatments, depending on the approved indication. It is administered intravenously as an infusion in its conventional formulation, under the supervision of qualified healthcare professionals. Treatment selection may require assessment of biomarkers, including PD-L1 expression or mismatch repair and microsatellite instability status, where relevant. Unlike conventional cytotoxic chemotherapy, pembrolizumab modifies immune signalling; consequently, it can cause inflammatory reactions affecting healthy organs. Appropriate patient selection, counselling and monitoring are essential throughout treatment.

Pembrolizumab was developed as a therapeutic antibody targeting the PD-1 immune checkpoint pathway, building on research demonstrating that tumours can evade immune surveillance by suppressing T-cell activity. The United States Food and Drug Administration (FDA) granted its first approval in September 2014 for advanced melanoma. The European Commission authorised Keytruda, the pembrolizumab reference product, for use in the European Union on 17 July 2015, following a positive assessment by the European Medicines Agency (EMA). Its clinical development included the KEYNOTE trial programme, which evaluated pembrolizumab across melanoma, lung cancer and numerous other malignancies, both as monotherapy and in combination regimens. Subsequent regulatory approvals expanded its use into additional tumour types, earlier treatment settings and selected biomarker-defined cancers. Approved indications and dosing recommendations vary between jurisdictions and evolve as new evidence becomes available. Current local prescribing information should therefore be consulted before treatment decisions are made.

Pembrolizumab is approved for selected patients with cancers including melanoma, non-small cell lung cancer, classical Hodgkin lymphoma, head and neck squamous cell carcinoma, urothelial carcinoma, renal cell carcinoma, endometrial carcinoma, cervical cancer, triple-negative breast cancer, oesophageal cancer, gastric or gastro-oesophageal junction cancer, colorectal cancer, hepatobiliary malignancies and other specified solid tumours. It is also used in certain patients with unresectable or metastatic cancers characterised by biomarkers such as microsatellite instability-high (MSI-H), deficient mismatch repair (dMMR) or elevated tumour mutational burden, where the relevant regulatory approval applies. Depending on the indication, it may be administered as monotherapy or combined with chemotherapy, targeted therapy or other anticancer agents. Selected indications include neoadjuvant treatment before surgery, adjuvant treatment after surgery and treatment of advanced disease. Eligibility can depend on tumour histology, stage, PD-L1 expression, molecular findings, previous treatment and surgical suitability. These uses are not universal across all countries or patient groups; clinicians should verify the applicable regulatory label and relevant clinical guidelines before prescribing.

Pembrolizumab is administered by intravenous infusion over approximately 30 minutes in its conventional formulation. Common adult regimens include a fixed dose of 200 mg every three weeks or 400 mg every six weeks, depending on the indication and approved prescribing schedule. For eligible paediatric patients, weight-based dosing may be used, subject to the applicable indication, age requirements and maximum approved dose. When pembrolizumab is combined with chemotherapy or another anticancer medicine, each component must follow its own prescribed schedule and administration requirements. Treatment duration depends on the indication, response, tolerability and protocol; many regimens have a defined maximum duration, while recurrence, disease progression or unacceptable toxicity may require earlier discontinuation. Clinicians should assess the patient before each administration and review symptoms, laboratory findings and evidence of immune-mediated toxicity. Dose reductions are generally not the standard approach for managing pembrolizumab toxicity; treatment may instead need to be withheld or permanently discontinued according to severity and prescribing guidance.

Common adverse effects of pembrolizumab include fatigue, itching, rash, diarrhoea, nausea, reduced appetite, musculoskeletal pain, cough and joint discomfort. Laboratory abnormalities, including changes in thyroid function, liver enzymes, blood glucose or kidney function, may also occur. When pembrolizumab is given with chemotherapy or other anticancer medicines, some adverse effects may arise from the combination, making attribution to an individual treatment difficult. Many mild effects can be managed with supportive care and clinical supervision, but persistent or worsening symptoms require assessment. Patients should be advised to report new symptoms rather than relying solely on their severity at onset, because immune-related reactions can initially appear mild and subsequently become more serious. The frequency and type of adverse effects vary according to the treatment regimen, cancer type, other medicines and individual patient factors.

Pembrolizumab can cause serious or potentially fatal immune-mediated adverse reactions when immune activation affects healthy tissues. These may include pneumonitis, colitis, hepatitis, nephritis, thyroid disorders, hypophysitis, adrenal insufficiency, type 1 diabetes mellitus and severe skin reactions. Less commonly, neurological, cardiac, haematological and other immune-mediated complications may occur. Severe infusion-related reactions are also possible. Toxicity may develop during treatment or after treatment has stopped. Patients should promptly report symptoms such as new or worsening breathlessness, persistent diarrhoea, severe abdominal pain, jaundice, marked weakness, confusion, unusual thirst or widespread skin changes. Depending on the affected organ and severity, management may require treatment interruption, permanent discontinuation, specialist evaluation and corticosteroids or other immunosuppressive treatment. Pembrolizumab should not be administered to patients with a known severe hypersensitivity to the medicine or its components. Clinicians must follow the relevant prescribing information for organ-specific assessment, treatment withholding and discontinuation criteria.

Before starting pembrolizumab, clinicians should review the patient's medical history, autoimmune disorders, organ transplantation history, previous immune-related toxicities, concomitant medicines and baseline organ function. Baseline assessments commonly include complete blood counts, liver and kidney function, thyroid function and blood glucose, with additional investigations guided by clinical circumstances. Patients with pre-existing autoimmune disease or a history of solid-organ transplantation require particular consideration because immune activation may exacerbate disease or increase the risk of graft rejection. Pregnancy status should be assessed where relevant, and patients should receive counselling about potential fetal harm and appropriate contraception according to the local prescribing information. Breastfeeding recommendations should also be discussed. Live vaccines are generally avoided during treatment unless specifically advised under applicable guidance; vaccination plans should be reviewed before therapy. Pembrolizumab is a monoclonal antibody cleared primarily through protein catabolism rather than conventional hepatic drug-metabolising pathways, so classic cytochrome P450-mediated pharmacokinetic interactions are uncommon. However, concomitant immunosuppressive medicines, corticosteroids and other anticancer therapies can influence treatment planning, immune activity or toxicity management. All concomitant medicines and supplements should be reviewed by the treating team.

Confirm the tumour type, disease stage, treatment intent and applicable approved indication before initiating pembrolizumab. Review required predictive biomarkers, such as PD-L1 expression or MSI-H/dMMR status, whenever specified by the relevant indication. Document baseline symptoms, autoimmune history, organ function and relevant laboratory results, and establish a monitoring plan before the first dose. Counsel patients and caregivers to report new respiratory symptoms, diarrhoea, abdominal pain, jaundice, endocrine symptoms, neurological changes or unusual fatigue promptly, even after treatment has ended. Explain that immune-mediated adverse events may require corticosteroids or specialist management rather than routine supportive treatment alone. Pharmacists should verify the prescribed regimen, infusion preparation, compatibility, storage and handling requirements against the product-specific information. Review concomitant chemotherapy, immunosuppressants and other medicines at each treatment cycle. Coordinate care with oncology nurses, laboratory services and relevant specialists to ensure timely investigation of suspected toxicities. Document treatment interruptions, adverse-event management and decisions about resuming therapy. Do not assume that the absence of symptoms excludes immune-related organ injury; scheduled clinical and laboratory monitoring remains important.