Toxicity and efficacy characterization of doxorubicin and trabectedin association versus doxorubicin alone in patients over 70 years with leiomyosarcoma: Analysis from LMS02 and LMS04 studies.

11515 Background: LMS02 (phase II) and LMS04 (randomized phase III) trials demonstrated the superiority of a combination regimen with Doxorubicin (Doxo, 60 mg/m²) and Trabectedin (Trab, 1.1 mg/m²) D1-D21 (Doxo+Trab) versus Doxorubicin (Doxo, 75 mg/m²) alone in the first line setting for metastatic or unresectable leiomyosarcomas with median Overall Survival (mOS) of 33 months (95% CI 26-48 months) versus 24 months (95% CI 19-31 months) (HR for death 0.65; 95% CI 0.44-0.95), respectively. The incidence of adverse events (AE), notably Grade 3-4 AE, was higher with the combination regimen compared to Doxo alone (97% versus 56%, p<0.001, respectively), although these were manageable. As more than one-third of soft-tissue sarcomas occur in patients (pts) over 65-year-old (yo), a better understanding of the risks and benefits of Doxo+Trab association in elderly patients is needed. Methods: Data from case report forms of pts aged ≥70 years enrolled in LMS02 and LMS04 were retrospectively analyzed to assess efficacy and toxicity of Doxo+Trab versus Doxo monotherapy. Results: 44 pts of 70 yo and older were included: 13 pts in LMS02 (Doxo+Trab 6 cycles, without maintenance), 15 pts in LMS04 arm B (Doxo+Trab : 6 cycles, followed by Trab maintenance for up to 17 cycles), and 16 pts in LMS04 arm A (Doxo monotherapy). The mean age was 74 yo (range 70-86), all pts had ECOG PS 0-1, and lung was the most frequent metastatic site. Median OS was 24 months with Doxo, 39 months with Doxo + Trab, and 48.9 months with Doxo + Trab-Trab (LMS04 cohort). Median PFS was 6.7 months with Doxo, 13.2 months in the Doxo + Trab arm, and 20.5 months with Doxo + Trab - Trab Toxicity analysis included patients from LMS02 and LMS04 as follows: 28 pts treated with Doxo+Trab (from both LMS02 and LMS04) and 16 pts treated with Doxo monotherapy in LMS04. The median number of received cycles was 6 in both groups. Twenty-two pts (80%) treated with the combination experienced Grade ≥3 AE, including 13 pts with Grade 4 events. These toxicities were predominantly hematologic; with 12% febrile neutropenia and 9% asthenia. In the monotherapy arm, ten pts (63%) had Grade ≥3 AE, including 5 pts with Grade 4 events, with asthenia (17%) and febrile neutropenia (17%) being the most frequent. The lack of statistical significance (p=0.2) should be interpreted cautiously due to limited sample size. Conclusions: For pts over 70 yo, the efficacy of the combination Doxo+Trab followed by trabectedin maintenance in advanced LMS in the first line setting, as measured by PFS and OS, did not differ from that in younger patients. Toxicity analysis suggests that age alone is not a limiting factor for this combination. Therefore, age-related frailty should not prevent patients from receiving a potentially life-prolonging treatment. A global geriatric evaluation and active supportive care may make treatment safer.