Abstract 2630: Meta-analysis of pazopanib and trabectedin in 2L+ metastatic synovial sarcoma (2L+ mSS)

Abstract

Abstract Background: Pazopanib (P) and trabectedin (T) are approved targeted treatments for metastatic soft tissue sarcoma (mSTS). Our objective was to evaluate the efficacy (from clinical trials [CT]) and effectiveness (from real-world studies [RW]) of P and T in second line (2L+) mSS. Methods: This meta-analysis included all English language studies assessing P or T efficacy/effectiveness in patients with 2L+ mSS, 1999 onwards, identified by a systematic literature review. Outcomes were overall response rate (ORR) representing the proportion of patients who have achieved CR or PR during the study and median overall survival (mOS) in months (mos) from start of study medication. Proportions from studies were pooled using generalized linear mixed models to account for small sample sizes, zero events and random site effects. Medians were combined using the weighted median of the medians method with 95% confidence intervals from an inverted sign test. Results: 16 studies with 405 patients with 2L+ mSS met the inclusion criteria. Response was measured variably across studies (CT: RECIST v1.0, v1.1; RW: modified RECIST or clinician assessment). ORR estimates were higher in RW than CTs (Table). OS results were consistent across CTs and RW (Table). Conclusions: This is the first study to provide estimates for patients with mSS in the 2L+ setting, distinct from mSTS and pool outcomes of targeted therapies. RW estimates of ORR for both treatments were higher than those observed in trials likely due to variable definition of response and in underlying prognostic factors. mOS was consistent across both types of studies and was similar to mOS seen on placebo (10.7 mos in PALETTE study) suggesting a high unmet need in this population. Funding: GSK (213368). Outcomes with pazopanib (P) and trabectedin (T) in clinical trials (CT) and real-world (RW) studiesPTP & T pooledORR-ALL (%)N=6, n=96, 18.9 (8.5, 41.8)N=7, n=162, 12.3 (8.0, 18.9)N=13, n=258, 14.7 (9.2, 23.4)ORR-CT (%)N=1, n=38, 13.2 (2.4, 23.9)†N=3, n=57, 7.0 (2.7, 18.1)N=4, n=95, 9.5 (5.1, 17.6)ORR-RW (%)N=5, n=58, 20.2 (7.4, 54.8)N=4, n=105, 15.2 (9.7, 23.9)N=9, n=163, 17.7 (9.9, 31.5)mOS-ALL (mos)N=4, n=96, 10.3 (8.7, 13.8)N=4, n=165, 9.9 (1.5, 13.9)N=8, n=261, 9.9 (9.2, 13.9)mOS-CT (mos)ND*ND*N=3, n=113, 10.3 (8.7, 13.9)mOS-RW (mos)ND*ND*N=5, n=148, 9.9 (9.2, 13.9)*Not done due to small sample size; †results of study since N=1. N=number of studies; n=number of patients. Estimates presented with 95% confidence intervals. Citation Format: Charlotte Carroll, Nashita Patel, Necdet B. Gunsoy, Dan Parks, Heide A. Stirnadel-Farrant, Shibani Pokras. Meta-analysis of pazopanib and trabectedin in 2L+ metastatic synovial sarcoma (2L+ mSS) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2630.