The approval of Keytruda, known by its generic name pembrolizumab, has introduced an option in cancer care. This treatment is a form of immunotherapy, a class of drugs that uses the body’s own immune system to combat cancer. While it has shown success across various cancer types, its application for pancreatic cancer is highly specific. It is not a universal treatment; its use is targeted to a select group of patients whose tumors exhibit particular biological characteristics, reflecting the move toward more personalized strategies.
How Keytruda Functions as Immunotherapy
The human immune system possesses cells called T-cells, which are designed to identify and eliminate threats, including cancerous cells. However, some cancer cells have developed a defense mechanism to evade this attack. They display a protein on their surface called PD-L1, which connects with a corresponding receptor, PD-1, on the surface of T-cells. This interaction acts like an “off-switch” or a brake, signaling the T-cell to leave the cancer cell alone.
Keytruda works as a PD-1 inhibitor, a type of drug known as a checkpoint inhibitor. It functions by blocking the PD-1 receptor on T-cells. By doing so, it prevents the PD-L1 on cancer cells from binding to it and deactivating the T-cell. This blockade “releases the brakes” on the immune system, allowing the T-cells to recognize the cancer cells as foreign and mount an attack to destroy them.
Patient Eligibility for Pancreatic Cancer
Before treatment can be considered, a patient’s tumor tissue must undergo specialized testing to identify certain genetic characteristics. The therapy is considered for patients with advanced pancreatic cancer that cannot be removed by surgery or has progressed after other treatments.
A primary qualification for Keytruda is a tumor that is identified as having high microsatellite instability (MSI-H) or being deficient in mismatch repair (dMMR). Mismatch repair is the body’s natural system for correcting errors that occur when DNA is copied in a cell. When this system is faulty (dMMR), it leads to an accumulation of errors in the DNA, particularly in short, repeated sequences of DNA called microsatellites, resulting in a state known as MSI-H. These numerous genetic mutations can produce abnormal proteins, making the cancer cells more conspicuous to the immune system once the PD-1/PD-L1 brake is released by Keytruda.
Another biomarker that can determine eligibility is a high tumor mutational burden (TMB-H). TMB-H indicates that the tumor’s cells have a large number of genetic mutations. A tumor is considered TMB-H if it has 10 or more mutations per megabase (mut/Mb) of DNA. Similar to MSI-H tumors, the high number of mutations in TMB-H tumors can create more neoantigens—new proteins that the immune system can recognize as foreign—thereby increasing the likelihood that immunotherapy will be effective.
Efficacy in Treating Pancreatic Cancer
For the specific group of pancreatic cancer patients with MSI-H/dMMR tumors, Keytruda has shown positive results. The KEYNOTE-158 trial, a phase II study, provided evidence for its approval. This study evaluated pembrolizumab in patients with various types of previously treated, advanced solid tumors that were MSI-H/dMMR, including a cohort with pancreatic cancer.
The study measured efficacy using the objective response rate (ORR), which is the percentage of patients whose tumors shrink significantly or disappear completely after treatment. Across all non-colorectal MSI-H/dMMR cancer types in the KEYNOTE-158 study, the ORR was 34.3%. For the patients who did respond to the treatment, the effects were often lasting. The study reported that the median duration of response had not been reached, suggesting that many responders experienced long-term benefits.
These positive outcomes are confined to the small percentage of pancreatic cancer patients with these specific biomarkers. For the majority of pancreatic cancer patients whose tumors do not have MSI-H, dMMR, or TMB-H characteristics, Keytruda has not demonstrated the same level of effectiveness.
Treatment Process and Potential Side Effects
Keytruda is administered to patients as an intravenous (IV) infusion in a clinical setting. A common schedule involves receiving the drug every 3 or 6 weeks. The treatment is given for up to two years or until the disease progresses or unacceptable side effects emerge.
Because Keytruda works by stimulating the immune system, its side effects are often immune-related, occurring when the newly activated immune system attacks healthy organs and tissues. Common side effects are often mild and manageable, and can include:
- Fatigue
- Skin rash
- Itching
- Diarrhea
- Nausea
More serious immune-related adverse events can occur, though they are less frequent. These can involve inflammation of various organs, such as:
- Lungs (pneumonitis)
- Colon (colitis)
- Liver (hepatitis)
- Hormone-producing glands like the thyroid
It is important for patients to report any new or worsening symptoms to their medical team immediately, as early intervention can be necessary. In some cases, treatment may need to be paused and corticosteroids administered to suppress the immune response.