In 2020, more than 1.9 million people globally were diagnosed with colorectal cancer, also known as colon cancer or bowel cancer. That number is projected to jump to 3.2 million colorectal cancer cases by 2040. Some people with colorectal cancer may have what’s known as mismatch repair deficient (dMMR) tumors with high microsatellite instability (MSI-H).
Mismatch repair (MMR) is a normal process that occurs in the body’s cells to correct any errors during DNA replication. Defects in the MMR process can lead to tumors with high microsatellite instability (MSI-H). Microsatellites are a short segment of DNA that repeats a number of times in a specific genomic location and are prone to mutations. About 15% of all colorectal cancer tumors are MSI-H. Past research shows that treating MMR deficient/MSI-High colorectal cancer tumors can sometimes be difficult.
Now, a new clinical study has found that giving the immunotherapy drug pembrolizumab before surgery instead of chemotherapy can help improve outcomes for people with stage two or three MMR deficient/MSI-High colorectal cancer. For this study, researchers recruited 32 study participants with stage two or stage three MMR deficient/MSI-High colorectal cancer.
Once a cancer is established in a person’s body it can already have spread to other parts of the body (stage 4) and even if detected early (stages 1-3), there is always a risk of disease recurrence afterward. Although researchers can use a traditional non-targeted treatment like chemotherapy and radiotherapy and certain targeted therapies to extend life, it usually becomes incurable, and most patients will eventually die from that cancer becoming resistant to these treatments.
They want to give ‘smarter’ drugs such as immunotherapy which has been particularly successful in treating patients with deficient dMMR bowel cancers which are stage 4 and is now the preferred treatment over chemotherapy as we can induce a remission in around a third of patients who are alive and well five years later rather than 10% or less. The NEOPRISM-CRC phase II clinical trial focused on the immunotherapy drug pembrolizumab, sold under the brand name Keytruda.
In June 2020, the U.S. FDA approved the use of pembrolizumab for treating patients with unresectable or metastatic MSI-H or dMMR colorectal cancer. Most cancer cells seem to be able to evade the patients’ normal immune system and keep growing and spreading. The immune system is very powerful as (it) is durable and to a degree has ‘memory’ to protect the body from cancer recurring beyond the duration of treatment which can be as short as a few weeks/month/years and very tolerable in terms of side effects. This is unlike chemotherapy or radiotherapy which although do kill rapidly growing cancer cells, are not targeted, and have many side effects so patients can usually only have a short course of this for a few months at a time.
Researchers found that more than 50% of participants treated with pembrolizumab before surgery had no signs of cancer after their surgery. The scientists compared these findings to previous studies showing only 4% of participants treated with chemotherapy before surgery were cancer-free after the surgery.
