Dostarlimab for the treatment of advanced endometrial cancer

Area of Science:

• Oncology
• Immunotherapy
• Genitourinary Cancers

Background:

• 20-30% of endometrial cancers (EC) exhibit mismatch repair deficiency (MMRd) or microsatellite instability-high (MSI-H), indicating sensitivity to immune checkpoint inhibitors.
• No standard treatment exists for advanced EC following progression on platinum-based chemotherapy.

Purpose of the Study:

• To assess the safety, tolerability, and antitumor activity of dostarlimab, an anti-PD1 therapy, in patients with advanced solid tumors.
• To evaluate dostarlimab in a specific cohort (A1) of patients with MMRd or MSI-H recurrent or advanced EC who progressed on platinum-containing regimens.

Main Methods:

• The GARNET trial, a phase I study, evaluated dostarlimab.
• The A1 cohort specifically enrolled patients with advanced or recurrent EC characterized by MMRd or MSI-H, who had prior platinum-based chemotherapy.

Main Results:

• Dostarlimab demonstrated significant clinical activity and durable responses in the A1 cohort.
• The treatment was well-tolerated, showing a favorable safety profile without compromising quality of life.
• These findings led to dostarlimab's accelerated approval for this patient population.

Conclusions:

• Dostarlimab monotherapy is recommended as the preferred treatment for advanced MMRd EC progressing after platinum-based chemotherapy, despite the absence of randomized trial data.
• Utilizing the MMRd biomarker for patient selection can optimize immunotherapy use, enhance healthcare system sustainability, and support personalized medicine by avoiding more toxic combination therapies.