A 100% effective drug against rectal cancer?

CANCER MEDICINE. 12 patients with rectal cancer, involved in a clinical trial, would have gone into remission after taking dostarlimab (a monoclonal antibody) for 6 months, indicates an American study published in the NEJM. What is this medicine? Its mode of action? Can it cure cancer 100%?

All patients (12 in number) of a cohort, suffering from a locally advanced rectal cancer entered in remissionafter participating in a clinical trialindicates an American study published in the New England Journal of Medicine on June 5, 2022. During this clinical trial, participants had to take during six months from dostarlimaba monoclonal antibody already used in endometrial cancer treatment. To date, none have had any side effects. What does this study say? What was the treatment exactly? What are the limitations of this trial? 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 advanced”who has deficient base mismatch repair (dMMR)/high microsatellite instability (MSI-H), progressing after or during platinum-based chemotherapy without any other treatment options“, says 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, on cancer research. These antibodies bind to PD-1, preventing mutual recognition between lymphocytes and cancer cells, thus allowing the immune cell to only hear signals that cause it to destroy the cancer cell.

How effective against rectal cancer?

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

In the prospective study published on June 5, 2022 in the NEJM, dostarlimab was administered as monotherapy every 3 weeks during 6 months in 12 patients with stage II or III rectal adenocarcinoma (rectal cancer or rectal cancer), in other words locally advanced. This treatment was originally to be followed by chemoradiotherapy and standard surgery (the classic treatments for rectal cancer). However, after six months of treatment and follow-up, the 12 patients either all the participants in the clinical trial – were in remission and did not present no more signs of tumor magnetic resonance imaging (MRI), endoscopy, digital rectal examination or biopsy. “At the time of this report, i.e. two years after the initial phaseno patient had received chemoradiotherapy or undergone 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. Nevertheless, 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 a breakthrough 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 rectal (non-metastatic) cancer has been improving for decades. The treatment of stage II and III rectal adenocarcinomas now systematically 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, the NEJM article reports.

What are the side effects of dostarlimab?

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

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

  • 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 suspended or permanently discontinued and treatment with corticosteroids (1 to 2 mg/kg/day of prednisone or equivalent) or any other appropriate treatment should be initiated, indicates the European Medicines Agency.

This treatment must be initiated and supervised by qualified medical specialists experienced in the treatment of cancer.

Is dostarlimab available in France?

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

What is the price of dostarlimab?

A 500mg/10ml 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 drugs, November 5, 2021

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