Updates from the GARNET trial underpin dostarlimab monotherapy as a meaningful treatment option for women with mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) advanced/recurrent endometrial cancer (A/R EC) who progressed after prior platinum therapy.
“At an impressive 6 years of follow-up, the high durable remission rate … was confirmed, with neither median duration of response (DoR) nor median overall survival (OS) being reached,” said Dr Bhavana Pothuri from New York University Langone Health, US, at ESMO Gynae 2026. There were clear plateaus in the Kaplan-Meier curves, beginning around the 2-year mark and extending through year 6 and beyond.
“Neither median DoR nor median OS was reached at a median follow-up of 69 months with single-agent immunotherapy—this is remarkable. These are pretreated patients experiencing a durable response and potentially being cured of their disease,” commented Dr Brian Slomovitz from Mount Sinai Medical Center, Miami Beach, Florida, US, in the ESMO press release.
The complete response (CR) rate of 16.1 percent (n=23) at the 2-year follow-up rose to 22.4 percent (n=32) after an additional 41 months of follow-up. This means that nine patients with a previous partial response achieved a CR at 6 years. “This is one of the most compelling findings from this long-term data … This increase shows that therapeutic response can continue to mature and deepen during extended follow-ups,” Pothuri explained.
The 2-year objective response and disease control rates remained stable at 6 years (45.5 percent and 60.1 percent, respectively). [ESMO Gynae 2026, abstract 69O]
In the conditional OS analysis, ≥86 percent of participants alive at 2 years were estimated to remain alive at 6 years. According to Pothuri, conditional OS is an invaluable tool that provides more relevant real-world data for patient counselling.
There were no new safety signals. Drug-related treatment-related adverse events (TRAEs) remained consistently low. The most common grade ≥3 TRAE was anaemia (5.2 percent). “[Most] patients who experienced toxicities did so early in their treatment course, with very few experiencing new toxicities later in time,” Pothuri said.
Similarly, there was a low incidence of treatment-related immune-related AEs (irAEs) despite extended long-term treatment. The most common grade ≥3 dostarlimab-related irAE was increased alanine aminotransferase level (2.6 percent).
Poor prognosis
Women with A/R EC have limited treatment options after progressing on frontline platinum-based chemotherapy, leading to poor prognosis. [N Engl J Med 2023;388:2145-2158]
Early GARNET data provide robust evidence of clinical benefit and durable antitumour activity with dostarlimab monotherapy, leading to global approvals in this setting. [JAMA Oncol 2020;6:1766-1772; J Immunother Cancer 2022;10:e003777]
The A1 cohort of GARNET comprised 143 women (median age 65 years) with dMMR/MSI-H EC. They received IV dostarlimab 500 mg Q3W for four cycles, followed by 1,000 mg Q6W for up to 2 years until disease progression, discontinuation, or withdrawal. Approximately one-third of participants received ≥2 prior lines of therapy.
The most common histological subtype was grade 1/2 endometrioid carcinoma (64.3 percent). Of note, nearly 15 percent presented with high-grade endometrioid carcinoma, and approximately 10 percent had aggressive, serous, or mixed carcinomas.
“Collectively, these robust data reinforce dostarlimab monotherapy as a highly effective standard of care treatment option for patients with dMMR/MSI-H A/R EC who have progressed following prior platinum-based therapy,” Pothuri said.
‘Hot’ tumours
“[These] are unprecedented results in the second-line management of EC … The data are game-changing, [with] a tremendous advantage for patients with dMMR/MSI-H or ‘hot’ tumours,” Slomovitz said.
“Immunotherapy has significantly changed the way we treat EC, and all patients—regardless of whether they have a ‘hot’ or ‘cold’ tumour—deserve to receive immunotherapy at some point during their treatment course. In the years ahead, the hope is that first-line immunotherapy, likely in combination with other novel agents, will negate the need for a second-line option by increasing the number of patients considered cured of their disease,” he added.