A revolutionary clinical trial? Posted on Sunday in new England Journal Of Medicine, a clinical trial carried out in the United States on 18 patients with colorectal cancer obtained surprising results: 100% cure. A revolution to qualify as it only affects about 5% of cases of locally advanced rectal cancer, explains Jean-Baptiste Bachet, a doctor at the department of hepato-gastroenterology and digestive oncology at the Pitié-Salpêtrière hospital in Paris, who responded to Release.
What is this clinical trial about?
These are 18 patients with rectal cancer who, for six months, received a dose of dostarlimab every three weeks. All 14 patients who completed the six months of treatment had a complete endoscopic clinical response and on imaging examinations, the tumor was gone! Dostarlimab is an anti-PD1 antibody, which falls within the field of immunotherapy: by inhibiting tumor defense mechanisms and activating the immune system, they help the body fight cancer on its own. Currently, 14 patients have been cured and 4 continue to be treated. All patients evaluated during this trial entered remission, with no serious side effects.
It’s a surprise ?
No, these results were quite expected compared to what we already knew, which does not prevent it from being a revolution even if it only affects 5% of rectal cancers. These rectal cancers are molecularly characterized as deficient in DNA mismatch repair (dMMR) enzymes and microsatellite sequence instability (MSI). They tend to be less responsive to chemotherapy and radiation therapy, increasing the risk that surgical treatment will be needed. Unfortunately, surgery can have significant health consequences: on the digestive and intestinal systems, but also sexual dysfunctions.
It’s obviously a game changer for the 5% of MSI rectal cancer patients and it will probably be a game changer for the 15% of MSI colon cancer patients too!
So it was an already known mode of treatment?
Yes, we had been trying to set up this trial in France for three years. In practice, these antibodies have shown very significant efficacy in patients with MSI metastatic colorectal cancer since 2015. And, in 2018, a Dutch study (named Niche) had already used antibodies in neoadjuvant (pre-operative) treatments in patients with localized MSI colon. cancer: most patients were in near complete clinical response, that is, there was no further tumor at the time of operation after only six weeks of treatment. Dostarlimab had already been used in France in patients with endometrial cancer in 2021, but the Haute Autorité de santé had issued an unfavorable opinion on the reimbursement of this molecule by social security due to lack of data on its efficacy.
And for the 95% of patients with another form of colorectal cancer?
No, this cannot refer to other cases of colorectal cancer because they are currently completely resistant to immunotherapy.
Whats Next ?
From now on, many more patients will have to be included, because with only 18 patients and very little follow-up (six months), the European Medicines Agency will probably not agree to an indication and reimbursement. In theory, five years of retrospective would be needed to speak of complete cure or remission, but the results of survival without recurrence of the disease at three years would already be extremely relevant, given the exceptional results of the study.
In the United States we know that there will be marketing and then the insurers will decide whether or not to reimburse the medicines -you still have to have insurance-, bringing the price of the medicine closer to 10,000 euros per dose. In Europe it is currently difficult to obtain indications and reimbursement without a comparative study, that is, without a comparison with standard treatment in a prospective multicentre study. In France, the short-term objective will be to create a prospective cohort in collaboration with the laboratory that markets dostarlimab so that patients can access treatment. In any case, the investigation will continue.
What other types of cancer might dostarlimab be effective for?
Dostarlimab belongs to the class of anti-PD1 and anti-PDL1 antibodies that currently includes a large number of molecules. The two most widely used anti-PD1 antibodies are pembrolizumab and nivolumab. They have proven their efficacy as monotherapy or in combination with chemotherapy in numerous cancers (melanoma, lung cancer, breast cancer, bladder cancer, colorectal cancer, stomach cancer, esophageal cancer, etc.). However, the greater efficacy of these antibodies has been described in cancers with the MSI/dMMR phenotype, regardless of their origin (colorectal, stomach, endometrial, etc.).