“All of the patients went into remission, without severe side effects” – Liberation

The use of the antibody dostarlimab has enabled 18 patients with colorectal cancer to achieve a cure, according to a study published Sunday in the United States. Jean-Baptiste Bachet, oncologist at Pitié-Salpêtrière, deciphers the advances that this therapy can offer.

A revolutionary clinical trial? Published Sunday in the New England Journal of Medicine, a clinical trial conducted in the United States on 18 patients with colorectal cancer obtained amazing results: 100% cure. A revolution to qualify since it only concerns about 5% of cases of locally advanced rectal cancer, explains Jean-Baptiste Bachet, doctor in the hepato-gastroenterology and digestive oncology department of the Pitié-Salpêtrière hospital in Paris, who responded to Release.

What is this clinical trial about?

It concerns 18 patients with rectal cancer who, for six months, received a dose of dostarlimab every three weeks. The 14 patients who completed the six months of treatment all had a complete clinical, endoscopic response and on imaging examinations, the tumor had disappeared! Dostarlimab is an anti-PD1 antibody, which falls within the scope of immunotherapy: by inhibiting tumor defense mechanisms and activating the immune system, they help the body fight cancer on its own. At present, 14 patients have been cured and 4 are still being treated. All of the patients tested during this trial went into remission, without severe side effects.

It is 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 concerns 5% of rectal cancers. These rectal cancers are molecularly characterized as being deficient in DNA mismatch repair (dMMR) enzymes and microsatellite sequence instability (MSI). They tend to be less responsive to chemotherapy and radiation therapy, which increases the risk that surgical treatment will be needed. Unfortunately, surgery can have significant consequences on health: on the digestive and intestinal systems, but also sexual dysfunctions.

So obviously it’s a revolution for the 5% of patients who have MSI rectal cancer and it will probably also be a revolution for the 15% of patients who have MSI colon cancer!

So it was a mode of treatment already known?

Yes, we had been trying to set up this trial in France for three years. In practice, these antibodies have demonstrated 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 treatments (before the operation) in patients with localized MSI colon cancer: the majority of patients were in almost complete clinical response, i.e. there was no more tumor at the time of the 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 a lack of data on its effectiveness.

And for the 95% of patients with another form of colorectal cancer?

No, this cannot concern other cases of colorectal cancer because they are currently completely resistant to immunotherapy.

What’s 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, it would take five years of hindsight to speak of cure or complete remission, but results of survival without recurrence of the disease after three years would already be extremely relevant, given the exceptional results of the study.

In the United States, we know that there will be a marketing and then the insurers will decide whether or not to reimburse the drugs – you still have to have insurance -, the price of the drug approaching 10,000 euros per dose. In Europe, it is currently difficult to obtain indications and reimbursements without a comparative study, that is to say without a comparison with the standard treatment in a prospective multicenter study. In France, the short-term objective will be to create a prospective cohort in partnership with the laboratory marketing dostarlimab so that patients can have access to treatment. In any case, the research will continue.

In what other type of cancer could dostarlimab be effective?

Dostarlimab belongs to the class of anti-PD1 and anti-PDL1 antibodies which currently include a large number of molecules. The two most commonly used anti-PD1 antibodies are pembrolizumab and nivolumab. They have demonstrated their effectiveness as monotherapy or in combination with chemotherapy in numerous cancers (melanoma, lung cancer, breast cancer, bladder cancer, colorectal cancer, stomach cancer, oesophageal cancer, etc.). Nevertheless, the greatest efficacy of these antibodies has been reported in cancers with the MSI/dMMR phenotype, regardless of their origin (colorectal, stomach, endometrium, etc.).


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