An Indirect Comparison of the Efficacy and Safety of Dostarlimab and Doxorubicin for the Treatment of Advanced and Recurrent Endometrial Cancer

Abstract

Background: There is no clear standard of care for advanced/recurrent endometrial cancer (EC) following platinum-based therapy. Dostarlimab is approved for patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) advanced/recurrent EC. This indirect treatment comparison (ITC) assessed dostarlimab efficacy and safety from the single-arm GARNET (NCT02715284) trial compared with doxorubicin from ZoptEC (NCT01767155).

Patients and methods: Patient-level data and study variables from GARNET Cohort A1 (dMMR/MSI-H EC) and the ZoptEC doxorubicin control arm were merged. Patients were matched based on eligibility criteria (main analysis population). Safety population included all patients who received treatment. The primary efficacy comparison outcome, overall survival (OS), was calculated using a Cox proportional hazards model, with adjusted stabilized inverse probability of treatment weighting. Modified assessment-scheduled matching Kaplan--Meier analysis was used for progression-free survival (PFS) and time to deterioration (TTD) in quality of life (QoL).

Results: In the main analysis population, median (95% CI) OS was not reached (NR; 18.0 months--NR) for dostarlimab (n = 92) and was 11.2 (10.0-13.1) months for doxorubicin (n = 233; HR: 0.41 [95% CI: 0.28-0.61]); median PFS was 12.2 (3.3-NR) and 4.9 (4.1-6.6) months, respectively. Median TTD in QoL was NR (2.5-NR; n = 61) and 4.5 (4.1-5.4; n = 188) months, respectively. Similar rates of adverse events (AEs, 11.6% vs 15.3%) and serious AEs (34.1% vs 30.1%) were observed with dostarlimab (n = 129) and doxorubicin (n = 249). Grade ≥3 AEs occurred in 48.1% vs 78.3%, respectively.

Conclusion: This ITC suggests a favorable benefit:risk profile for dostarlimab in patients with dMMR/MSI-H advanced/recurrent EC.

Keywords: DNA mismatch repair; doxorubicin; endometrial neoplasms; immune checkpoint inhibitors; microsatellite instability; uterine neoplasms.

© The Author(s) 2022. Published by Oxford University Press.

Figures

Figure 1.

Flow diagram showing patient attrition for each analysis set for (A) GARNET and (B) ZoptEC.

Figure 2.

Adjusted* overall survival (A), progression-free survival (B), duration of response (C), and time-to-deterioration in QoL (D) for the main analysis data set. Abbreviations: CI, confidence interval; DoR, duration of response; IPTW, inverse probability of treatment weighting; NR, not reached; OS, overall survival; PFS, progression-free survival; QoL, quality of life; TTD, time to deterioration. *The number of patients at risk with IPTW adjustment differs slightly from the total sample size due to weighting by IPTW. The total numbers of patients and those after applying the stabilized IPTW were as follows (dostarlimab/doxorubicin): for OS and PFS, 92/233 and 91/233; for DoR, 40/31 and 40/32; and for TTD in QoL, 62/188 and 61/188. The weighted IPTW number at risk has been rounded to the nearest integer value. As the results of the proportionality test showed a P-value greater than .05 (P = .096), an adjusted analysis utilizing a Cox proportional hazards model with stabilized IPTW was used for OS analysis.