One Step Closer: Immunotherapy VS Humankind’s Long-Standing Foe
Cancer remains a disease affecting millions of lives with no definite cure, and each year, 45 000 Americans are diagnosed with rectal cancer. As the search for the cure to cancer continues, a recent clinical trial conducted by investigators at the Memorial Sloan Kettering Cancer Center (MSK) sheds light on an experimental drug that carries promising results. What does this mean for humankind’s fight against their long-standing foe?
How Immunotherapy Works
Immune cells contain checkpoints that turn on to recognize foreign cells and prevent them from attacking normal cells. However, cancer cells can shut down immune cells in order to let tumours hide and grow. But, in comes immunotherapy, a groundbreaking treatment method used for cancer. With the specific type of immunotherapy used in this trial, an agent called the checkpoint inhibitor is used to release the immune cell’s brake to allow it to recognize and attack cancer cells.
The MSK Clinical Trial
Led by Dr. Cercek and Dr. Diaz, the research team premised their investigation around two key ideas. First, they wanted to determine which specific group of patients would benefit most from the immunotherapy approach. This certain subset of patients says Dr. Diaz, are those with rectal cancer that has metastasized, with mismatch repair-deficient (MMRd) tumours which an estimated 5%-10% of all rectal cancer patients have. Rectal tumours that are MMRd regarding metastatic disease are especially responsive to immunotherapy. More specifically, MMRd colorectal cancer is sensitive to the programmed death 1 (PD-1) inhibitor. Second, the team wanted to avoid the toxicity that comes as a side effect of rectal cancer treatment. With this goal in mind, Dr. Cercek also proposed to not put patients through chemotherapy, radiation, and surgery if the immunotherapy was successful in making their cancer disappear, and to closely monitor them instead. However, if surgery was ever needed, the doctors believed that immunotherapy would facilitate the surgery by shrinking the tumour.
So what was the method behind their life-changing work? To participate, all patients had to have stage 2 or 3 locally advanced rectal cancer with tumours that are MMRd. Patients were administered an anti-PD-1 monoclonal antibody called dostarlimab intravenously, every 3 weeks for the duration of six months. After the treatment, standard chemoradiotherapy and surgery followed, but these procedures were not used for patients who exhibited a clinical complete response following the completion of the immunotherapy.
Hopeful Results
The results of the clinical trial were exciting, to say the least: out of the 12 patients that completed the treatment, no tumour could be found in any of the 12 patients. Thus far, no progression or recurrence of cancer has been detected during their follow-up. Furthermore, no patient received chemoradiotherapy or surgery. The results: a 100% success rate.
What’s Next?
The researchers continue to investigate this treatment method, enrolling patients with gastric, prostate, and pancreatic cancers to see whether it would prove beneficial to apply this method of using immunotherapy to other cancers with MMRd tumours and life-changing treatment side effects. Dr. Diaz has used the term “immunoablative” therapy to describe this method of applying immunotherapy as one that is capable of removing cancer in place of surgery, chemotherapy, and radiation. Dr. Diaz leaves us with a hopeful remark regarding this treatment: “That might sound futuristic — but in this trial, we have a clinical example where that happened.” As humankind continues the fight against cancer, perhaps the MSK rectal cancer trial — with a method of treatment proving to have remarkable results — brings us one step closer to a groundbreaking cure.
About the Author
Selina Liu is a grade 10 student based in Ontario. She is passionate about the sciences and wants to pursue a career in the medical field. In her spare time, you can find her playing the violin, drawing, or reading.
Sources
https://www.nejm.org/doi/full/10.1056/NEJMoa2201445
https://www.mskcc.org/news/rectal-cancer-disappears-after-experimental-use-immunotherapy
