On February 9, 2023, dostarlimab-gxly was granted regular approval for adults with mismatch repair–deficient (dMMR) recurrent or advanced endometrial cancer, as determined by a U.S. Food and Drug Administration–approved test, whose disease has progressed on or following a prior platinum-containing regimen in any setting and who are not candidates for curative surgery or radiation therapy.1 The agent received accelerated approval in this setting in April 2021.
Supporting Efficacy Data
Regular approval was based on findings in a cohort of the GARNET trial (ClinicalTrials.gov identifier NCT02715284), consisting of 141 patients with dMMR recurrent or advanced endometrial cancer whose disease had progressed on or after a platinum-containing regimen. Patients received intravenous dostarlimab at 500 mg every 3 weeks for four doses followed by 1,000 mg every 6 weeks until disease progression or unacceptable toxicity.
OF NOTE
Dostarlimab-gxly has warnings/precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.The objective response rate on blinded independent central review was 45.4% (95% confidence interval = 37%–54%), with a complete response in 15.6% of patients. Median duration of response was not reached (range = 1.2+ to 52.8+ months); responses persisted for at least 12 and at least 24 months in 85.9% and 54.7% of responders, respectively.
How It Is Used
The recommended dosage for the first four doses is 500 mg every 3 weeks. Subsequent dosing, beginning 3 weeks after the fourth dose, is 1,000 mg every 6 weeks until disease progression or unacceptable toxicity.
No dose reductions for dostarlimab are recommended. Product labeling provides instructions on dosage modification for immune-mediated adverse reactions and infusion-related reactions.
Safety Profile
Safety data come from 150 patients in the GARNET cohort who received at least one dose of dostarlimab. The most common adverse events of any grade were fatigue/asthenia (49%), anemia (35%), nausea (32%), diarrhea (29%), constipation (23%), vomiting (23%), and rash (21%). The most common grade 3 or 4 adverse events included anemia (18%), increased transaminases (4%), and urinary tract infection (4%). The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes (15%), decreased sodium (5%), and increased alanine aminotransferase (4.7%).
Serious adverse events occurred in 38% of patients, most commonly urinary tract infection (4%), sepsis (3.3%), acute kidney injury (2.7%), and abdominal pain (2.7%). Adverse events led to treatment discontinuation in 10%, including increased transaminases, sepsis, bronchitis, pneumonitis, rash, pruritus, pancreatitis, encephalitis, and nephritis. Adverse events led to death in one patient (because of concurrent immune-mediated encephalitis and urinary tract infection).
Dostarlimab has warnings/precautions for immune-mediated adverse reactions (including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis with renal dysfunction, dermatologic reactions, and solid organ transplantation rejection), infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving dostarlimab.
REFERENCE
1. Jemperli (dostarlimab-gxly) injection, for intravenous use, prescribing information, GlaxoSmithKline, February 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761174s003s004lbl.pdf. Accessed February 17, 2023.
