Dostarlimab: miracle drug against rectal cancer?

Dostarlimab is a monoclonal antibody used in immunotherapy in the endometrial cancer treatment. In June 2022, the results of a US clinical trial published in the New England Journal of Medicine show that theall patients (12 in number) of a cohort, suffering from a locally advanced rectal cancer entry in remission, after being treated with dostarlimab. How is it possible ? What are the effects of this drug on cancer cells? What side effects? Is it sold in France? What we know so far.

Definition: what is dostarlimab?

Dostarlimab is a monoclonal antibody used in immunotherapy. It is indicated in monotherapy for the treatment of adult patients affected byendometrial cancerrecurrent or advancedwho have poor base mismatch repair (dMMR)/microsatellite instability high (MSI-H), progressing after or during platinum-based chemotherapy without any other treatment optionssays the European Medicines Agency (EMA).

How does dostarlimab work?

Dostarlimab is a monoclonal antibody that blocks PD-1 protein, well known for its role in moderating the immune reaction, explains the Arc Foundation, in cancer research. These antibodies bind to PD-1, preventing mutual recognition between lymphocytes and cancer cells, allowing the immune cell to it only listens for signals that cause it to destroy the cancer cell.

How effective against rectal cancer?

Locally advanced rectal cancer would be very sensitive to PD-1 protein blockade in monotherapy

In the prospective study published June 5, 2022 in the NEJM, dostarlimab was administered as monotherapy every 3 weeks for 6 months in 12 patients with stage II or III rectal adenocarcinoma (rectal cancer or cancer of the rectum), In other words locally advanced. Originally, this treatment was to be followed by chemoradiation therapy and standard surgery (the classic treatments for rectal cancer). However, after six months of treatment and follow-up, the 12 patients – either all participants in the clinical trial – were in remission and I do not present no more signs of tumor magnetic resonance imaging (MRI), endoscopy, digital rectal examination, or biopsy. “At the time of this report, that is, two years after the initial phaseno patient had received chemoradiation therapy or surgery, and no cases of progression or recurrence were reported during follow-up. None adverse event Grade 3 or higher has not been reported. It can be concluded that locally advanced rectal cancer would be very sensitive to blockade of the PD-1 protein in monotherapy“, detail the authors of the study. However, the cohort being very restricted (only 12 participants), the results of this study seem limited, even if they are encouraging. Longer follow-up would be needed to assess the duration of the immune response. “This research has provided what may be the first glimpse of an innovative treatment […] Such an approach cannot yet supplant our current approach to curative treatment.” confirms Dr. Hanna Sanoff, in an article shared in addition to the study.

The cure rate for (non-metastatic) rectal cancer has been improving for decades. Treatment of stage II and III rectal adenocarcinomas now routinely includes surgery, radiotherapy and chemotherapy. Such treatment has resulted in a 3-year disease-free survival rate of up to 77%. However, this therapeutic approach is exhausting and can lead to significant long-term sequelaeincluding neuropathy, infertility, and bowel and sexual dysfunction, reports the NEJM article.

What are the side effects of dostarlimab?

Depending on the severity of the adverse effect, treatment with dostarlimab should be discontinued or definitively discontinued and treatment with corticosteroids

Immune-related adverse reactions, potentially serious or even fatal, may occur in patients receiving dostarlimab. For example :

• Immune-related pneumonitis (about 1.4% of patients)
• Immune-related colitis (about 1.6% of patients)
• Immune-related hepatitis (about 0.2% of patients)
• Hypothyroidism (about 7.2% of patients)
• Hyperthyroidism (about 1.9% of patients)
• Adrenal insufficiency (about 1.4% of patients)
• Immune-related nephritis (about 0.6% of patients)
• Immune-related rash (about 3% of patients)
• Immune-related arthralgia (about 4% of patients)
• Infusion-related reactions (approximately 1.4% of patients)

Depending on the severity of the adverse effect, treatment with dostarlimab should be discontinued. definitively suspended or discontinued and treatment with corticosteroids (1 to 2 mg/kg/day of prednisone or equivalent) or any other appropriate treatment should be started, indicates the European Medicines Agency.

The drug exists in France under the name Jemperli.

Is Dostarlimab available in France?

dostarlimab is marketed in France for a long time and administered in the form of infusion solution (intravenous infusion): Jemperli® (500mg)indicated in oncology. is a drug list 1Then subject to medical prescription. This treatment must be initiated and supervised by Qualified medical specialists with experience in treating cancer. In 2021, the treatment received an unfavorable opinion regarding its reimbursement by Social Security by the High Health Authority, justifying “lack of robust comparative data to assess the contribution of JEMPERLI (dostarlimab) versus available alternatives, in particular chemotherapy”, “the very preliminary nature of the available efficacy data” Y “marked toxicity by an incidence of serious adverse events (AEs) reported in one-third of patients (34%) and grade ≥ 3 AEs in nearly one in two patients (48.1%).“

What is the price of dostarlimab?

A 500 mg/10 mL vial of dostarlimab (Jemperli®) would cost between 6,800 and 10,000 euros.

Sources: Study: PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer, NEJM, June 5, 2022 / European Medicines Agency (EMA) Website / JEMPERLI 500 mg (dostarlimab), Haute Autorité de Santé, Opinion on medications, November 5, 2021