Keytruda, also known as pembrolizumab, is an immunotherapy drug used in cancer treatment. It works by leveraging the body’s own immune system to identify and combat cancer cells. Keytruda functions as a programmed cell death protein 1 (PD-1) inhibitor, allowing immune cells to recognize and attack tumors more effectively.
Keytruda’s Role in Treating Colon Cancer
Keytruda is used in colon cancer treatment for patients whose tumors exhibit specific genetic characteristics. These include microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) tumors. Approximately 10-15% of colorectal cancer patients have tumors with these biomarkers. This type of cancer has a defect in the DNA repair mechanism, leading to a higher number of genetic mutations.
Keytruda works by blocking the PD-1 pathway, a mechanism cancer cells use to hide from the immune system. By inhibiting PD-1, Keytruda removes the “brakes” on the immune system, allowing T-cells to mount a stronger anti-tumor response. This approach makes it effective in advanced or metastatic colon or rectal cancer that cannot be surgically removed. It may also be considered as a first-line treatment option for these patients.
Measuring Keytruda’s Impact on Survival
The effectiveness of Keytruda in colon cancer patients with MSI-H/dMMR tumors is measured by several metrics, including Overall Survival (OS), Progression-Free Survival (PFS), and Overall Response Rate (ORR). Overall Survival refers to the length of time a patient lives from the start of treatment. Progression-Free Survival indicates how long a patient lives without their cancer growing or spreading. Overall Response Rate measures the percentage of patients whose tumors shrink or disappear after treatment.
Clinical trials have demonstrated Keytruda’s impact. In the Phase 3 KEYNOTE-177 trial, Keytruda improved progression-free survival as a first-line treatment for unresectable or metastatic MSI-H or dMMR colorectal cancer. The median PFS for patients on Keytruda was 16.5 months, compared to 8.2 months for those receiving chemotherapy. At 12 and 24 months, the PFS rates were 55.3% and 48.3% with Keytruda, respectively, versus 37.3% and 18.6% with chemotherapy. The ORR for Keytruda in this trial was 44%, with 11% of patients achieving a complete response and 32.7% a partial response.
The KEYNOTE-164 trial supported these findings in previously treated MSI-H/dMMR advanced or metastatic colorectal cancer. This Phase 2 study showed an objective response rate of 33%. The median overall survival in one cohort was 31.4 months, with estimated 12- and 24-month OS rates of 72% and 55%, respectively. Many patients experienced durable responses, with some lasting longer than two years. Individual outcomes can vary based on factors such as cancer stage, prior treatments, and patient characteristics.
What to Know About Keytruda Treatment
Keytruda is administered as an intravenous (IV) infusion every 3 to 6 weeks, depending on the cancer type. Each infusion takes about 30 minutes. The duration of treatment varies, but patients receive Keytruda for up to two years, or as long as it remains effective and side effects are manageable.
Patients undergoing Keytruda treatment may experience side effects, as the drug can cause the immune system to attack healthy tissues. Common side effects include:
- Fatigue
- Diarrhea
- Rash
- Nausea
- Abdominal pain
- Muscle or bone pain
- Fever
- Decreased appetite
More serious, though less common, immune-mediated adverse reactions can involve inflammation in various organs, such as the lungs (pneumonitis), colon (colitis), liver (hepatitis), or endocrine glands (thyroid problems).
Patients should communicate any new or worsening symptoms to their healthcare team promptly, as early management of side effects can prevent them from becoming severe. Healthcare providers monitor patients for infusion reactions during treatment and for other side effects that may occur weeks or even months after starting or stopping Keytruda. Discussion with an oncologist about all treatment options and personalized care is recommended.