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Rectal cancers disappear in a dostarlimab experimental drug trial

A new drug trial has eliminated 100% of rectal tumours in patients after 6 months. Published in the New England Journal of Medicine, the study involved a small cohort of 12 patients who had advanced stage II or III rectal cancer and the drug dostarlimab. Researchers from Yale University School of Medicine trialled a new blockade treatment and found that all patients in the study had tumours eliminated and did not need chemotherapy or surgery afterwards.

Chemotherapy consequences

The standard treatment for locally advanced rectal cancer is chemotherapy with the goal of shrinking a tumour or stopping the spread of cancer. Chemotherapy delivered before surgery aims to make surgery less invasive and more effective. However, chemotherapy is marked with complications and toxic effects. Bowel dysfunction and infertility are often unfortunate consequences from chemotherapy. Rectal surgery is invasive and may warrant a permanent diverting colostomy. Patients see long-lasting consequences even after recovery from rectal cancer.

Any treatment options that reduce the need for surgery or chemotherapy will offer patients a better recovery and quality of life.

Mismatch repair

Furthering the need for new approaches, some rectal tumours have been shown to respond poorly to standard chemotherapy treatments. For example, approximately 5 to 10% of rectal cancers are mismatch repair deficient, and these are very hard to treat with chemotherapy.

However, mismatch repair deficient cancers have been shown to be responsive to programmed death 1 (PD-1) blockade in the context of metastatic disease.

Dostarlimab is an anti–PD-1 monoclonal antibody approved by the US Food and Drug Administration. It is currently used to treat endometrial cancers with mismatch repair deficiency. The team hypothesized that Dostarlimab could be effective in rectal cancer patients too.

Tumour free, chemo free, surgery free

A total of 16 patients were enrolled and treated in the trial. To date, 12 have been enrolled for longer than 6 months and have completed nine cycles of treatment.

Patients received dostarlimab for 6 months, with doses administered every 3 weeks. The status of patents’ tumours were monitored throughout using

The study aimed to follow up the treatment with standard chemoradiotherapy and surgery as required. It was not required.

The results are very promising. All 12 patients had a clinical complete response, with no evidence of tumours found on magnetic resonance imaging (MRI), endoscopic evaluation or biopsy. In addition, the therapeutic responses were rapid, with resolution of symptoms within just 9 weeks after initiation. At the time of this report, no patients had received chemoradiotherapy or surgery.

Some side effects were reported, including rashes and fatigue in some patients, but the authors note that no adverse effects higher than grade 3 were reported. Furthermore, no cases of progression or recurrence of tumours had been reported during the follow-up.

No patients have withdrawn from the study. The remaining 4 patients of the 16 have received at least 1 dose and continue to receive the treatment.

Next steps

It is worth noting that these are preliminary results and the trial is expected to include about 30 patients.

Dostarlimab and other PD-1 blockade options will be evaluated in further mismatch repair deficient tumours, including pancreatic, gastric, and prostate cancers.

“Although the results of our study are promising, especially given that 12 consecutive patients all had a clinical complete response, the study is small and represents the experience of a single institution,” the authors note. “These findings must be reproduced in a larger prospective cohort that balances academic and community practices and ensures the participation of patients from a diverse set of racial and ethnic backgrounds.”

Written by Poppy Jayne Morgan, Front Line Genomics

Image Credit: Canva