First-line doxorubicin plus trabectedin effective, safe for metastatic leiomyosarcoma
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Doxorubicin in combination with trabectedin appeared to be an effective and safe first-line therapy for metastatic leiomyosarcoma, according to results of the phase 2 LMS-02 study presented during the ASCO20 Virtual Scientific Program.
“Soft tissue sarcomas are rare and heterogeneous tumors with differences in clinical behavior and genetic variances,” Patricia Pautier, MD, medical oncologist at Institut Gustave Roussy in France, said during a presentation. “Uterine leiomyosarcoma and soft tissue leiomyosarcoma are rare tumors with a poor prognosis when locally advanced or metastatic. They also have moderate chemosensitivity.”
Previous studies have shown overall response rates for combination therapies given in the first-line setting of less than 50% for uterine leiomyosarcoma (U-LMS) and 35% for soft tissue leiomyosarcoma (ST-LMS), with a mean response duration of 3 months to 6 months and no impact on OS.
The antitumor drug trabectedin (Yondelis; Janssen, PharmaMar) has demonstrated activity in leiomyosarcoma after anthracycline failure. The single-arm LMS-02 study examined the drug in combination with doxorubicin as first-line treatment for metastatic/advanced U-LMS and ST-LMS.
Results of LMS-02 published in 2015 showed an ORR of 59.6% among patients with U-LMS and 39.3% among patients with ST-LMS, with manageable toxicity.
At ASCO, Pautier and colleagues presented updated PFS and final OS results of the study, which included 108 patients (median age, 59 years) with leiomyosarcoma (U-LMS, n = 47; ST-LMS, n = 61). Most patients (85%) had metastatic disease.
Patients received doxorubicin dosed at 60 mg/m2 followed by trabectedin dosed at 1.1 mg/m² on day 1 and pegfilgrastim on day 2 every 3 weeks for up to six cycles.
Researchers stratified patients into U-LMS and ST-LMS groups and permitted surgery for residual disease.
Seventy-seven patients (71.3%) received all six cycles of treatment and 20 patients (18.5%) had metastasis resection.
Median follow-up was 7.2 years.
Results showed median PFS of 10.1 months (95% CI, 8.5-12.6) and median OS of 34.4 months (95% CI, 26.9-42.7) among all patients.
Patients with metastatic U-LMS had a poorer prognosis that those with ST-LMS, according to researchers. Median PFS among the U-LMS group was 8.3 months (95% CI, 7.4-10.3) compared with 12.9 months (95% CI, 9.2-14.1) in the ST-LMS group. Median OS was 27.5 months (95% CI, 17.9-38.2) in the U-LMS group vs. 38.7 months (95% CI, 31-52.9) in the ST-LMS group.
Median OS among the 20 patients who underwent surgery was not reached compared with 31.6 months (95% CI, 23.9-35.4) for those who did not undergo surgery
“In this homogeneous series of patients with metastatic uterine and soft tissue LMS, efficacy and results of trabectedin in combination with doxorubicin in first-line therapy are very encouraging,” Pautier said. “Results of a phase 3 trial comparing this combination followed by trabectedin or doxorubicin alone as a first-line therapy in metastatic LMS are pending.” – by John DeRosier
References:
Pautier P, et al. Abstract 11506. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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Pautier P, et al. Abstract 11506. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
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