Real-world outcomes of doxorubicin plus trabectedin (D+T) in leiomyosarcoma (LMS).

Abstract

e23536 Background: LMS-04 trial shows improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) with D+T followed by trabectedin (T) alone compared with doxorubicin alone in advanced LMS. Real-world outcomes with this regimen remain limited. This single-center retrospective study reports on the standard-of-care use of D+T in localized and advanced uterine LMS (ULMS) and soft-tissue LMS (STLMS). Methods: We included patients with confirmed histologic diagnosis of LMS treated with D+T at any point in routine clinical practice at MD Anderson Cancer Center (MDACC). The objective was to assess recurrence-free survival (RFS)/PFS, OS, ORR, and toxicity for both advanced and localized LMS patients treated with D+T in a real-world setting. Kaplan Meier method and log rank tests were used to assess survival outcomes and compare outcomes in subgroups. Data collection is ongoing with over 100 patients to date. Results: Fifty patients were included in this primary analysis (26 with ULMS, 24 with STLMS, cf. Table). In STLMS, primary tumor location was retroperitoneum in 20% (n=10), visceral in 10% (n=5), limb in 10% (n=5), abdominal wall in 4% (n=2), and scalp in 4% (n=2). In those with advanced LMS (n=40), median PFS was 10.5mo, PFS at 1 year was 37%. Overall, the ORR was 42% (21/50), and 40% (16/40) in patients with advanced disease. Median PFS for patients with advanced ULMS and STLMS was 9.6mo and 11mo months, respectively (p=0.73). Among 10 patients with localized disease, 5 underwent surgery before D+T (1 STLMS, 4 ULMS), and 6 received post-induction local therapy, including surgery alone (2 STLMS, 1 ULMS) or surgery and radiotherapy (3 STLMS). Nine patients with advanced disease received post-induction local therapy with surgery alone (1 ULMS, 4 STLMS), surgery plus radiotherapy (1 ULMS, 1 STLMS), surgery plus ablation (1 STLMS), or ablation alone (1 ULMS), with median PFS not reached (NR) versus 8.6 months in those without local therapy (p=0.011). Median OS for patients with advanced disease was 32.6mo. Grade ≥3 toxicity occurred in 92% (46/50), with 46% (23/50) requiring dose reductions; common toxicities were anemia, fatigue, and thrombocytopenia. Conclusions: In a real-world setting, outcomes with D+T are consistent with LMS-04 for ORR though slightly inferior in PFS for ULMS. We observe improved PFS in patients receiving local treatments after induction. ORR, toxicity, and dose-reduction rates were also comparable. Updated results with larger cohorts will be presented. Localized ULMS (N=5) Advanced ULMS (N=21) Localized STLMS (N=5) Advanced STLMS (N=19) Median age, yrs 45 48 49 54 Gender - - 60% F40% M 53% F47% M Size≥10 cm 4 (80%) 13 (62%) 3 (60%) 4 (21%) ORR 40% 42.9% 60.0% 36.8% RFS/PFS, mo (95% CI) 9.7 (5.1 – NR) 9.6 (4.5 – 14.7) NR 11 (8.6 – 16.6) RFS/PFS at 12 mo 40% 40.4% 100% 34.2% OS, mo NR 22.5 NR 32.6 Dose reduction, N (%) 2 (40%) 10 (48%) 2 (40%) 9 (48%) % of grade ≥3 toxicity 100% 90.5% 80.0% 89.5%