FDA approves immunotherapy that can spare rectal cancer surgery

The US Food and Drug Administration (FDA) has approved an immunotherapy that may allow some people with rectal cancer to skip chemotherapy, radiotherapy and surgery altogether. On 19 October 2026 the agency granted accelerated approval to dostarlimab (Jemperli) for adults with locally advanced rectal cancer whose tumours are mismatch repair deficient (dMMR) or microsatellite instability high (MSI-H).

The approval covers dostarlimab used alone as the first treatment for previously untreated stage II or III disease, confirmed by an FDA-authorised test.

Why this group of patients is different

Standard treatment for locally advanced rectal cancer usually involves chemotherapy and radiotherapy followed by surgery to remove the rectum. Surgery often means a stoma bag, which may be temporary or permanent. Treatment can also cause lasting problems with bowel, bladder and sexual function, and infertility.

A small share of rectal cancers have a fault in the cell's DNA repair system, described as dMMR or MSI-H. These tumours carry many mutations, which makes them easier for the immune system to recognise once its brakes are released. The FDA estimates that about 3% of locally advanced rectal cancers are dMMR or MSI-H. GSK, which makes dostarlimab, puts the figure at 5% to 10% of rectal cancers overall.

Dostarlimab is a PD-1 checkpoint inhibitor. It blocks a signal that tumours use to switch off immune T cells.

The evidence behind the approval

The approval rests on the AZUR-1 trial (NCT05723562), led by GSK. This phase 2 study enrolled 154 patients with dMMR or MSI-H stage II or III rectal cancer. Each received dostarlimab 500 mg by infusion every three weeks for nine cycles, about six months.

The main measure was a sustained clinical complete response at 12 months. That means no sign of cancer on examination, endoscopy and MRI, a year after finishing dostarlimab. Patients with a complete response were monitored closely instead of having surgery.

Key results reported by the FDA and GSK:

• 71% of patients received dostarlimab alone, with no other treatment, and had no disease progression
• 47% (54 of 116 evaluable patients) had a sustained complete response at 12 months by central review
• 68% (98 of 144) had a sustained complete response at 12 months by investigator assessment
• the overall response rate was 79% by central review and 82% by investigators
• of 15 patients who went on to surgery, 12 had no cancer left in the removed tissue

GSK reported the full AZUR-1 results at ESMO 2026 on 24 October, with publication in Annals of Oncology. At a median follow-up of 26.3 months, no patient with a complete response had seen their disease progress.

The FDA also considered a study at Memorial Sloan Kettering Cancer Center (NCT04165772). Of 50 patients, 93% had a sustained complete response at 12 months. Among 27 people followed for at least three years, one had a local recurrence.

"For certain types of rectal cancer, this approval represents a groundbreaking option that avoids surgery, radiation and chemotherapy," said Angelo de Claro, director of the FDA's Oncology Center of Excellence.

Why the two complete response figures differ

The 47% figure comes from an independent central review, and the 68% figure from the doctors running the trial. Central reviewers judge scans and endoscopy images without seeing the patient, and the number of patients who could be evaluated also differed. The FDA lists the central review figure as the key result.

Side effects

The most common side effects in AZUR-1 were fatigue (32%), rash (22%), diarrhoea (18%) and itching (17%). Serious reactions occurred in 20% of patients, and 3% stopped treatment because of side effects.

Like other checkpoint inhibitors, dostarlimab can cause the immune system to attack healthy organs, and the FDA notes these reactions can be severe or fatal.

What accelerated approval means

Accelerated approval lets the FDA approve a drug based on an early measure, here the 12-month complete response, that is reasonably likely to predict longer-term benefit. Continued approval depends on further evidence, such as longer follow-up confirming that people stay cancer free.

The FDA reviewed the application with a national priority voucher and completed it four months ahead of its target date. The review was carried out under Project Orbis, a programme for sharing cancer drug reviews between regulators. The UK's MHRA was part of this review, which was still ongoing at the time of the announcement.

Points to keep in mind

• Testing is essential. Only tumours confirmed as dMMR or MSI-H qualify. Most rectal cancers are not in this group.
• Close monitoring. Patients who skip surgery need regular MRI scans and endoscopy for years so any regrowth can be caught early.
• Follow-up is still short. Two years of AZUR-1 follow-up is encouraging, but long-term survival data are still to come.
• The confidence interval. For the 47% central review figure, the FDA and GSK publish different lower confidence limits (27% and 37%). The point estimate is the same in both.
• Not yet in the UK or EU. At the time of writing, this use was approved only in the US.

This article explains research findings and is not medical advice. If you have rectal cancer, ask your team whether your tumour has been tested for dMMR or MSI-H.