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Checkmate to Colorectal Cancer by Checkpoint Inhibitor

Cancers of the colon and rectum, together known as colorectal cancer can be fatal and impact thousands of individuals across the globe. The National Cancer Institute has estimated that, in 2022, there would be 151,030 new colorectal cancer cases and 52,580 deaths from colorectal cancer in the United States (US).

When it comes to colorectal cancer treatment, the American Cancer Society has mentioned that the treatment approach largely depends on the cancer stage. Surgical excision is the primary treatment approach when colorectal cancer has not spread to other sites, with probable additional treatments such as chemotherapy and radiation. Immunotherapy has revolutionized cancer treatment and immune checkpoint inhibitors, a major component of immunotherapy must be looked at.

In a recent study published in The New England Journal of Medicine, researchers found that the use of involving immune checkpoint inhibitors could be highly beneficial in managing rectal cancer patients and could completely eradicate malignant cells. The treatment could effective enough to eliminate the need for surgeries. The study comprised 12 adult participants with a locally advanced, mismatch repair (MMR)-deficient rectal cancer of stage I or stage II. Scientists theorized that this type of cancer could be effectively treated using a type of immunotherapy which helps the human body detect and combat cancer cells in a more effective manner.

The research team used an immune checkpoint inhibitor known as dostarlimab, which is a programmed cell death protein 1 (PD-1) inhibitor. Anti-PD-1 therapy is aimed at preventing immune evasion of cancer cells. Participants received dostarlimab intravenously (i.v.) every three weeks for about six months.

The study participants responded well to dostarlimab treatment. Importantly, none of the participants had any evidence of a tumor by the end of the clinical trial, and none of them needed to undergo additional chemotherapy or surgery after the trial. To date, all the study participants have completed six months of follow-up.

Prof. John Bridgewater, a clinical researcher from the University College London Cancer Institute who specialized in gastrointestinal medical oncology, and was not involved in the trial, said, “These data report the highly effective use of immunotherapy, specifically, an inhibitor of the checkpoint called the programmed death receptor 1 (PD1) in patients with mismatch repair-deficient rectal cancer […] This is a significant advance in that it obviates the need for surgery or radiation therapy for these cancers, both conventional treatments with many complications and side effects.”

The authors of the present study have stated that “These findings must be reproduced in a larger prospective cohort that balances academic and community practices and ensures the participation of patients from a diverse set of racial and ethnic backgrounds.”

Dr. Dahut pointed out that the study adds to the growing evidence that understanding the cancer type could impact treatment. He said that, “Patients should really be empowered to understand the biology of their cancer. Work was done that let patients know that they had a particular subtype of rectal cancer. It really shows the power of biomarkers and precision medicine. If you treated all patients with rectal cancer with a checkpoint inhibitor, you wouldn’t see this response rate. So wherever patients are, it’s important that they’re talking to their doctors and learning as much about their cancer as they can. Their therapies may be vastly different based on those results.”

Conclusion

The study findings showed that immune checkpoint inhibitors could effectively eradicate tumor cells from patients with colorectal cancers and the results are better among MMR genetic abnormality patients; however, larger sample sizes and longer duration of follow-up assessments are required to validate the study’s findings. Further research must be conducted to determine the reason of low efficacy of immune checkpoints in metastatic colorectal cancers.

Author

Pooja Toshniwal Paharia

Dr. Pooja Toshniwal Paharia is a Consultant Oral and Maxillofacial Physician and Radiologist, M.DS (Oral Medicine and Radiology) from Mumbai. She strongly believes in evidence-based radiodiagnosis and therapeutic regimens for benign, potentially malignant, or malignant lesions and conditions either arising from the oral and maxillofacial structures or manifesting in the associated regions.

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