Jubilee Brown, MD from the Levine Cancer Institute, and Division of Gynecologic Oncology, Atrium Health speaks about Clinical Activity and Safety of the Anti-Programmed Death 1 Monoclonal Antibody Dostarlimab for Patients With Recurrent or Advanced Mismatch Repair-Deficient Endometrial Cancer: A Nonrandomized Phase 1 Clinical Trial.
Link to Abstract:
https://pubmed.ncbi.nlm.nih.gov/33001143/
Abstract:
Importance:
Endometrial tumors with faulty mismatch mutation repair systems may be more susceptible to anti-programmed death 1 (PD-1) treatments. Dostarlimab (TSR-042) is an anti-PD-1 antibody that binds to the PD-1 receptor with a high affinity.
Objective:
Dostarlimab’s anticancer efficacy and safety in patients with defective mismatch repair endometrial cancer were investigated.
Participants, setting, and design:
On March 7, 2016, part 1 of this continuing, open-label, single-group, multicenter research began, and on May 8, 2017, patients with defective mismatch mutation repair endometrial cancer began enrolling. The average period of follow-up was 11.2 months (range, 0.03 [ongoing] to 22.11 [ongoing] months; based on radiological assessments). The statistical study was carried out between July 8 and August 9, 2019.
Interventions:
Patients were given 500 mg of dostarlimab intravenously every three weeks for four doses, followed by 1000 mg every six weeks until disease progression, therapy cessation, or withdrawal.
The following are the main outcomes and measures:
The primary end aim was a blinded independent central evaluation of the objective response rate and duration of response using Response Evaluation Criteria in Solid Tumors, version 1.1.
Results:
104 women with inadequate mismatch mutation repair endometrial malignancies were enrolled and treated with dostarlimab as of the data cutoff (median age, 64.0 years [range, 38-80 years]). 71 of them were included in the study because they showed detectable illness at baseline and after 6 months or more of follow-up. 30 patients had a confirmed response (objective response rate: 42.3 percent; 95 percent confidence interval: 30.6 percent-54.6 percent); 9 patients (12.7 percent) had a confirmed full response, and 21 patients (29.6%) had a confirmed partial response. Responses were long-lasting; the median response time was not attained (median follow-up was 11.2 months). At 6 months, the chance of sustaining a response was 96.4 percent, and at 12 months, it was 76.8%. The most prevalent grade 3 or higher treatment-related adverse events were anemia (3 of 104 [2.9 percent ]), colitis (2 of 104 [1.9 percent ]), and diarrhea (2 of 104 [1.9 percent ].
Conclusions and applicability:
Dostarlimab was found to have clinically significant and long-lasting anticancer efficacy, as well as an acceptable safety profile, in patients with defective mismatch mutation repair endometrial malignancies who had previously received platinum-based chemotherapy.
Trial registration: ClinicalTrials.gov identifier: NCT02715284:
http://clinicaltrials.gov/show/NCT02715284