A small clinical trial with 12 participants yielded impressive results: 100% of the colorectal cancer patients saw their cancer disappear. So how does this immunotherapy-based treatment work so effectively?
Of all rectal cancers, adenocarcinomas are the most common. To treat them, oncologists usually suggest surgery to remove the cancerous area, followed by chemotherapy. However, immunotherapy could replace this cumbersome protocol for patients. A small clinical trial conducted at Memorial Sloane Kettering Cancer Center in New York showed impressive results: 100% of the patients in the trial went into remission without the need for surgery or chemotherapy after treatment with the therapeutic antibody Dostarlimab.
In a small group of 12 patients with stage II or III rectal adenocarcinoma, Dostarlimab achieved tumor eradication after one injection every three weeks for six months. In 100% of patients, the tumor was undetectable on CT, MRI, endoscopy, and rectal biopsies. They did not need surgery or chemotherapy to complement the effect of Dostarlimab. No patient relapsed during the follow-up period, which lasted from 6 to 25 months. Dostarlimab did not cause serious side effects in most patients, only rash, fatigue, nausea, and pruritus. Only one person developed a non-life-threatening thyroid problem.
Dostarlimab also offers hope to people with Lynch syndrome as eight of the 12 participants in the clinical trial had it. This inherited disease dramatically increases the lifetime risk of developing bowel cancer and is associated with worse outcomes after surgery and chemotherapy. Indeed immunotherapy may be a promising tool for treating patients with Lynch syndrome.
This approach only works in so-called Mismatch Repair–Deficient colorectal cancer, which accounts for 10-15% of rectal adenocarcinomas diagnosed each year. Dostarlimab is an antibody that prevents the recognition of the PD-1 receptor, present on T cells, with its ligand PDL-1, present on cancer cells. The interaction of the receptor with its ligand paralyzes the immune response: instead of destroying the abnormal cell, the T cell spares it. By mechanically blocking this interaction, Dostarlimab enables the T cells to destroy the abnormal cell.
These are impressive results that should be replicated in future independent, multi-participant clinical trials. The question of the durability of the results will also be crucial; even if participants have been in remission for several months, there is no guarantee that they will still be in remission several years from now.