Clinical trials have many endpoints – or milestones they are looking to achieve. These endpoints help signify the safety, efficacy, and tolerability of the treatments. In the Phase 3 KEYNOTE-394 clinical trial, which was evaluating KEYTRUDA (pembrolizumab) for Asian patients with advanced hepatocellular carcinoma, one such endpoint was overall survival (OS). According to biopharmaceutical company Merck, the trial achieved this endpoint, meaning that KEYTRUDA, in patients previously treated with sorafenib, significantly benefited patients. As hepatocellular carcinoma is often diagnosed late, patients have poor prognoses; KEYTRUDA could potentially fill this unmet need and improve patient outcomes.

KEYTRUDA

So what exactly is KEYTRUDA? According to Chemocare, KEYTRUDA is:

a highly selective humanized monoclonal IgG4 antibody directed against the PD-1 receptor on the cell surface. The drug blocks the PD-1 receptor, preventing binding and activation of PD-L1 and PD-L2, [which] causes the activation of T-cell mediated immune responses against tumor cells.

The treatment is administered as a 100mg intravenous injectable. 3 years ago, the FDA granted Accelerated Approval to KEYTRUDA for patients with previously treated hepatocellular carcinoma. Beyond hepatocellular carcinoma, KEYTRUDA is also indicated in the United States for the treatment of:

• Unresectable or metastatic melanoma
• Metastatic non-squamous non-small cell lung cancer (NSCLC) with no EGFR or ALK mutations
• Unresectable head and neck squamous cell carcinoma
• Metastatic NSCLC with PD-L1 expressing tumors
• Cervical cancer
• Merkel cell carcinoma (MCC)
• Renal cell carcinoma (RCC)
• MSI-H or dMMR colorectal cancer
• Cutaneous squamous cell carcinoma (cSCC)
• Triple-negative breast cancer
• HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma
• Urothelial carcinoma
• Classic Hodgkin’s lymphoma
• Primary mediastinal large B-cell lymphoma (PMBCL)

KEYNOTE-394 Clinical Trial

Most recently, researchers evaluated KEYTRUDA plus supportive care as opposed to a placebo plus supportive care within the KEYNOTE-394 clinical trial. Altogether, 453 patients enrolled. During the trial, patients received up to 35 cycles of KEYTRUDA treatments. Ultimately, KEYTRUDA was shown to improve overall survival for patients with previously treated hepatocellular carcinoma. Additionally, KEYTRUDA treatment also improved progression-free survival and overall response rate compared to the placebo.

Adverse Reactions to KEYTRUDA

Although KEYTRUDA is relatively safe and well-tolerated, some adverse effects have been observed throughout a variety of clinical trials for multiple conditions. These include:

• Allergic reactions
• Appetite loss
• Nausea and vomiting
• Shortness of breath
• Rash
• Cough
• Fever
• Fatigue
• Diarrhea or constipation
• Colitis
• Neutropenia (low white blood cell count)
• Pneumonitis
• Polyneuropathy
• Sepsis
• Pleural effusion
• Adrenal insufficiency
• Hypo- or hyperparathyroidism
• Pneumonia
• Cardiac failure
• Autoimmune hepatitis

If taking KEYTRUDA and experiencing any of these adverse reactions, please speak to your healthcare provider.

Hepatocellular Carcinoma

Hepatocellular carcinoma is a form of rare liver cancer, though it is the most common subtype of primary liver cancer. Unlike other secondary liver cancers, which spread from other organs, hepatocellular carcinoma begins in the liver. Risk factors include hepatitis B or C infections, obesity, heavy alcohol consumption, diabetes, or having a pre-existing liver condition. Unfortunately, this particular cancer is often not diagnosed until later stages. Because of this, prognosis is poor, with a 5-year survival rate of under 15%. Patients may be asymptomatic until later stages. However, as the cancer progresses, symptoms may include:

• Unintended weight loss
• Appetite loss
• Fatigue and/or general malaise
• Nausea and vomiting
• Abdominal pain, lump, or heaviness (upper right)
• Pale and chalky bowel movements
• Dark urine

Currently, liver transplants are the best treatment option for patients with hepatocellular carcinoma. Thus, KEYTRUDA represents an opportunity to provide better therapeutic options to patients.

Learn more about hepatocellular carcinoma here.