2025 Southeastern Residency Conference

Title: Comparison of Dostarlimab to Pembrolizumab in Combination with Chemotherapy in Patients with Advanced or Recurrent Endometrial Cancer

Authors: Aaliyah Parchment, Stephen Tomasek, Sarah Gifford, Nhi Tran, Joann Gold

Background/Purpose: Carboplatin and paclitaxel, combined with either dostarlimab or pembrolizumab, are National Comphrehensive Cancer Network approved standard-of-care regimens for the first line treatment of stage III or IV or recurrent endometrial cancer. However, despite the widespread use of dostarlimab and pembrolizumab, no clinical studies have been conducted to directly compare these two agents head-to-head when combined with cytotoxic chemotherapy. The objective of this study is to compare the efficacy and safety of dostarlimab and pembrolizumab when used in conjunction with carboplatin and paclitaxel for the first-line treatment of patients with stage III or IV endometrial cancer and those experiencing their first recurrence of the disease.

Methodology: This study is a retrospective chart review conducted at AdventHealth to compare the impact of dostarlimab and pembrolizumab with concurrent chemotherapy. The study has received approval from the Institutional Review Board. Those included in the study are patients with advanced or recurrent endometrial cancer who have received dostarlimab or pembrolizumab in combination with carboplatin and paclitaxel within AdventHealth from August 1, 2022, to January 31, 2024. Patients included are women 18 years of age and older with historical confirmed diagnosis of primary stage III or IV endometrial cancer, or first recurrence of disease. Patients with more than one recurrence of endometrial cancer will be excluded. Data collection from the electronic medical record will include patient demographics (age, race), tumor characteristics (histology type, stage at diagnosis, microsatellite instability status/mismatch repair status), and any prior therapies.  

The primary outcome is rate of progression free survival (PFS), defined as the proportion of patients who remained alive and without disease
 progression. The secondary outcome is overall survival (OS), measured as the duration from the initiation of treatment to death from any cause. Safety outcomes will be evaluated by common side effects associated with immunotherapy. The primary, secondary, and safety outcomes will be analyzed by basic statistical analyses. 

Results: Baseline characteristics, including age, treatment history, and molecular profiles, were similar between groups. Median progression-free survival (PFS) was 144 days (95% CI, 106.58–181.42) in the dostarlimab group and 173 days (95% CI, 0.00–379.44) in the pembrolizumab group; this difference was not statistically significant (P = 0.656). No deaths occurred in the pembrolizumab group, limiting overall survival (OS) comparison. Adverse events occurred in all patients. Treatment interruptions were more frequent with pembrolizumab (20% vs. 5%, P = 0.034). Constipation (P = 0.027) and myalgia (P = 0.023) were significantly more common in the pembrolizumab group, while grade ≥3 anemia was more frequent in the dostarlimab group (P = 0.006).

Conclusion: Dostarlimab and pembrolizumab demonstrated similar PFS outcomes, with no significant differences observed. The absence of deaths in the pembrolizumab group limited OS comparisons. Pembrolizumab was linked to more frequent treatment delays and gastrointestinal and musculoskeletal adverse events, while dostarlimab was associated with a higher rate of severe anemia. Overall, both regimens had comparable safety profiles. Further investigation in larger cohorts is warranted to confirm these findings.

Presentation Objective: Identify clinical data comparing dostarlimab to pembrolizumab with chemotherapy in advanced endometrial cancer

Self-Assessment Question: 
Which of the following correctly describes the intervention arm of the RUBY trial for first-line therapy in advanced or recurrent endometrial cancer?
A. Pembrolizumab 200 mg + chemotherapy for 6 cycles q3w, followed by pembrolizumab 400 mg q6w
B. Dostarlimab 500 mg + chemotherapy for 6 cycles q3w, followed by dostarlimab 1000 mg q6w up to 3 years
C. Chemotherapy alone for 6 cycles
D. Dostarlimab 1000 mg q3w + chemotherapy, followed by pembrolizumab 400 mg