On May 23, 2017, Keytruda was granted accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of solid tumors with a specific genetic marker, including prostate cancer.
The drug is still under investigation for other types of prostate cancer.
How Keytruda works
As an immunotherapy, Keytruda does not directly act on the tumor, but instead boosts the body’s own immune system to fight cancer cells.
The immune system is capable of identifying and destroying abnormal or infected cells using T-cells, a type of white blood cell involved in immune response. However, some types of prostate cancer cells can evade being detected by the immune system and continue to grow.
To prevent T-cells from accidentally causing damage to healthy cells, there are immune system checkpoints in place, including the PD-1 pathway. T-cells have a receptor called programmed cell death 1 (PD-1) on their surface. When PD-1 interacts with specific ligands such as PD-L1 or PD-L2, it sends a message to the T-cells, blocking them from attacking.
These ligands are normally found on the surface of healthy cells. But some types of cancer can take advantage of this system by making PD-L1. When the T-cells come in contact with these cancer cells, they mistake them for healthy cells and don’t attack them.
Keytruda is a monoclonal antibody designed to bind to and prevent PD-1 from interacting with its ligands. With its PD-1 blocked, the T-cells can identify and destroy the cancer cells. However, as Keytruda acts to remove an immune system checkpoint, it can also cause T-cells to attack healthy cells.
Keytruda in clinical trials for prostate cancer
Keytruda has been and is being tested in several completed and ongoing clinical trials for prostate cancer, alone and in combination with other drugs.
Results from a Phase 2 trial (NCT02312557) carried out by the OHSU Knight Cancer Institute demonstrated that Keytruda could be effective in advanced prostate cancer patients treated with Xtandi (enzalutamide). The trial, which is still recruiting patients at a site in Oregon, aims to treat 58 patients.
Patients will receive Keytruda once every three weeks for four treatment cycles, along with standard-of-care Xtandi. Following a monitoring phase, patients will receive four more doses of Keytruda, then will be followed for up to two and a half years.
Data from the first 10 men, whose cancer was continuing to progress on Xtandi but who were treated as part of the trial, were published in the medical journal Oncotarget. Three of these 10 men responded to Keytruda, with a decrease in prostate-specific antigen (PSA), a marker associated with prostate cancer, to almost undetectable levels in their blood. One patient’s PSA levels decreased from 2,503 to 0.1 ng/ml, an unprecedented reduction. All three of these patients remained free of progression at their last reported follow-up. Two of them also saw a reduction in their tumor size and symptoms.
However, not all patients responded to the drug, and researchers are uncertain which factors could influence this. Future studies are being planned by OHSU.
- As part of their extensive Keynote clinical trials program, Merck is currently recruiting participants with metastatic castrate-resistant prostate cancer (mCRPC) across North America, Europe, and Asia for three ongoing Keynote studies in prostate cancer: the Phase 1 Keynote-365 trial (NCT02861573), the Phase 2 Keynote-199 trial (NCT02787005), and the Phase 1/2 Keynote-046 (NCT02325557) trial, which is sponsored by Advaxis and is testing their drug candidate ADXS31-142 alone or in combination with Keytruda.
Keytruda is administered as an infusion into the bloodstream over 30 minutes.
Common side effects seen with Keytruda treatment include fatigue, itchy skin, diarrhea, decreased appetite, rash, fever, cough, difficulty breathing, bone and muscle pain, constipation and nausea. Keytruda could also cause more serious immune system conditions that damage healthy tissues, resulting in inflammation of organs including the lungs, colon, liver, endocrine glands, and kidneys.
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