Outcomes of dostarlimab versus chemotherapy in post-platinum patients with recurrent/advanced endometrial cancer: data from the GARNET trial and the National Cancer Registration Service in England.

OBJECTIVES: Immune checkpoint inhibitors have emerged as novel treatment options in patients with endometrial cancer. In this study we aimed to compare the survival outcomes of patients with recurrent or advanced endometrial cancer. These patients had received dostarlimab after platinum-based chemotherapy in the single-arm, Phase I GARNET trial. We compared them with a matched indirect real-world cohort. METHODS: The real-world cohort was established using National Cancer Registration and Analysis Service data, with five treatment-specific real-world sub-cohorts identified. To compare clinical outcomes between the GARNET trial and real-world cohorts, we performed matching-adjusted indirect comparisons. We used prognostic variables to create matching scenarios, including scenario 1 that incorporated grade, histology, and platinum-based chemotherapy number; scenario 2 that considered histology and platinum-based chemotherapy number; and scenario 3 that included race/ethnicity, stage at diagnosis, histology, and prior surgery. Overall survival was defined as the time between the first dostarlimab dose or second-line real-world treatment and death. Adjusted hazard ratios for matching-adjusted indirect comparisons were estimated via weighted Cox proportional-hazards models. Progression-free survival, using time-to-next treatment as a proxy for real-world cohorts, was summarized descriptively. RESULTS: Distribution of baseline characteristics that were matched was similar between the GARNET cohort (n=153) and the real-world cohort (n=999). The most common International Federation of Gynecology and Obstetrics (FIGO) stage in both cohorts was stage III/IV (n=88; 57.5% and n=778; 77.9%, respectively), with endometroid histology predominating in the GARNET cohort (n=121; 79.1%) and non-endometrioid the predominant form in the real-world cohort (n=575; 57.6%). The median overall survival for dostarlimab was longer (range 27.1-40.5 months [95% confidence interval (CI) 6.4-non-estimable and 19.4-non-estimable]) both before and after matching for all scenarios compared with the real-world cohort (10.3 months). Across all matching scenarios, patients in the GARNET cohort had a decreased risk of death, with a HR for overall survival of 0.32 (p<0.0001) before matching, as compared with the overall real-world cohort and most treatment-specific real-world cohorts. For all three scenarios, progression-free survival rates at 12 and 18 months were higher for patients on dostarlimab compared with the real-world cohort (0.48 and 0.43 respectively before matching in the GARNET cohort vs 0.28 and 0.16 respectively in the real-world cohort; using time to next treatment as proxy). The effective sample size for scenario 1 was low when compared with the other scenarios (scenario 1: n=18; scenario 2: n=62; scenario 3: n=67). CONCLUSION: In this adjusted indirect dataset, patients with recurrent/advanced mismatch repair deficient/microsatellite instability-high endometrial cancer post-platinum-based chemotherapy who received dostarlimab in the GARNET trial had significantly improved overall survival compared with patients receiving current second-line treatment in England.

Previously treated recurrent or advanced endometrial cancer in England: A real-world observational analysis.

OBJECTIVES: In patients with recurrent/advanced endometrial cancer who have progressed after first-line treatment, there are a lack of real-world data on treatment patterns, characteristics, and survival outcomes. A novel study was conducted to determine real-world treatment patterns and outcomes in England. METHODS: This non-interventional study used routine, administrative health data from the National Cancer Registration and Analysis Service in England to identify patients diagnosed with recurrent/advanced endometrial cancer between 1 January 2013 and 31 December 2018, inclusive. A cohort of patients who progressed to second-line treatment were identified as the 'immune checkpoint inhibitor-eligible second-line' cohort. The co-primary objectives were to summarise baseline demographics, disease characteristics, treatments received, and depict overall survival and time-to-next-treatment (a proxy for progression-free survival) from the start of second-line therapy using Kaplan-Meier methodology. RESULTS: Overall, 12,058 patients were diagnosed with recurrent/advanced endometrial cancer; 999 patients were included in the immune checkpoint inhibitor-eligible second-line cohort and 77.9% (778 of 999) had advanced disease (Stage III/IV). The most common treatments received at second-line were carboplatin plus paclitaxel (27.9%), carboplatin plus liposomal doxorubicin (14.1%), liposomal doxorubicin monotherapy (13.0%), and paclitaxel monotherapy (11.6%). From initiation of second-line therapy, median (95% confidence interval) overall survival was 10.3 months (9.2-11.1), and median time-to-next-treatment was 7.7 months (7.1-8.2). CONCLUSIONS: Treatments received in the relapsed setting were variable and survival outcomes poor at second-line, highlighting the need for standard of care guidance and innovative therapies to improve patient outcomes in England and in countries with similar treatment patterns. FUNDING: GSK.