A new clinical trial 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. This comes as past research shows that treating MMR deficient/MSI-High colorectal cancer tumors can sometimes be difficult. The study, presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2024, focused on the immunotherapy drug pembrolizumab, sold under the brand name Keytruda. The NEOPRISM-CRC phase II clinical trial recruited 32 study participants with stage two or stage three MMR deficient/MSI-High colorectal cancer and found that more than 50% of participants treated with pembrolizumab before surgery had no signs of cancer after their surgery, compared to only 4% of those treated with chemotherapy before surgery.
Colorectal cancer, also known as colon cancer or bowel cancer, is a prevalent type of cancer that is projected to increase globally. Some people with colorectal cancer may have mismatch repair deficient (dMMR) tumors with high microsatellite instability (MSI-H). MSI-H is a result of defects in the MMR process, which can lead to tumors with mutations in microsatellites, a short segment of DNA that repeats in a specific genomic location. About 15% of all colorectal cancer tumors are MSI-High, and while traditional treatments like chemotherapy and radiotherapy can help extend life, they often become incurable as the cancer develops resistance. Immunotherapy has shown promise in treating MMR deficient/MSI-High colorectal cancer, with pembrolizumab now being approved for such cases by the U.S. FDA.
Researchers hope that by giving immunotherapy such as pembrolizumab before surgery, they can shrink the cancer significantly and eliminate microscopic cancer cells in the bloodstream or lymphatic system, potentially curing patients upfront and avoiding the need for post-operative standard chemotherapy. The NEOPRISM-CRC trial aims to enroll more patients to validate their findings and examine the long-term relapse survival rate. Additionally, they have incorporated translational objectives into the trial to understand the biology of dMMR cancers and optimize immunotherapy treatment for long-term remission or even cure. The results have raised interest among experts, with Anton Bilchik, MD, PhD, noting that this is the first study to investigate immunotherapy in these early stages of colon cancer, showing a high percentage of patients having no tumor in the specimen after treatment.
Glenn S. Parker, MD, FACS, FASCRS, adds that while the results of immunotherapy before surgery in colorectal cancer are promising, it is crucial to continue long-term follow-up to assess the duration of response and to determine if these findings can be applicable to all colon cancers. As new drugs for both chemotherapy and immunotherapy are developed, clinical trials will play a significant role in tailoring treatment based on the molecular genetic profile of individual patients and their tumors, leading to greater precision medicine in the future. This innovative approach to using pembrolizumab in stage two or three MMR deficient/MSI-High colorectal cancer patients before surgery offers a new avenue for improving outcomes and potentially curing this type of cancer.
In conclusion, the NEOPRISM-CRC phase II clinical trial has shown that giving pembrolizumab before surgery instead of chemotherapy can significantly improve outcomes for people with stage two or three MMR deficient/MSI-High colorectal cancer. The results of the study have led researchers to explore the potential of upfront immunotherapy in shrinking the cancer and eliminating microscopic cancer cells to prevent future relapse. As more patients are enrolled in the trial and additional translational objectives are pursued, the goal is to better understand the biology of dMMR cancers and optimize immunotherapy treatment for long-term remission or even cure. While experts acknowledge the promising results, further research and long-term follow-up are necessary to assess the durability of response in these patients and to determine the applicability of this approach to all types of colon cancer. As precision medicine continues to evolve, incorporating both chemotherapy and immunotherapy based on individual genetic profiles, clinical trials will play a crucial role in shaping the future of cancer treatment.
