Clinical Scorecard: FDA approves dostarlimab for advanced rectal cancer

At a Glance

Key Highlights

• FDA granted accelerated approval to dostarlimab-gxly (Jemperli) for the specified adult population.
• In AZUR-1, 47% of 116 evaluable patients achieved a sustained clinical complete response for 12 months.
• In AZUR-1, the objective response rate was 79%; 110 of 154 treated patients (71%) received dostarlimab alone without additional cancer treatment or disease progression.
• In a separate investigator-led, single-arm trial, the sustained clinical complete response rate was 93% and the objective response rate was 100%.
• Both supporting studies lacked randomized comparators; longer follow-up is needed to establish response durability.

Guideline-Based Recommendations

Diagnosis

• Confirm MSI-H or dMMR status using an FDA-authorized test for solid tumors.

Management

• Administer dostarlimab-gxly 500 mg intravenously every 3 weeks for up to 9 cycles, until disease progression or unacceptable toxicity.
• In AZUR-1, assess tumor response using endoscopy, rectal MRI, and CT imaging.
• In AZUR-1, patients achieving clinical complete response entered nonoperative management with close surveillance; patients without complete response or with recurrent or progressive disease were evaluated for standard treatment.

Monitoring & Follow-up

• The prescribing information advises monitoring liver enzymes, creatinine, and thyroid function during treatment.
• In AZUR-1, surveillance for patients achieving clinical complete response was every 4 months for the first 2 years and every 6 months thereafter.

Risks

• The prescribing information warns of potentially severe or fatal immune-mediated adverse reactions and infusion-related reactions.
• Warnings also include complications following allogeneic hematopoietic stem cell transplantation and embryo-fetal toxicity.

Patient & Prescribing Data

Adults with previously untreated MSI-H/dMMR stage II/III locally advanced rectal cancer.

The approved regimen is 500 mg intravenously every 3 weeks for up to 9 cycles, until progression or unacceptable toxicity. In AZUR-1, 110 of 154 treated patients (71%) received dostarlimab alone without additional cancer treatment or disease progression.

Clinical Best Practices

• Use an FDA-authorized test to establish MSI-H or dMMR status.
• In AZUR-1, response was assessed with endoscopy, rectal MRI, and CT imaging.
• The prescribing information advises monitoring liver enzymes, creatinine, and thyroid function during treatment.
• In AZUR-1, patients managed nonoperatively after clinical complete response underwent close surveillance.

Related Resources & Content

• FDA
• DailyMed