Trabectedin for Patients with Advanced Soft Tissue Sarcoma: A Non-Interventional, Retrospective, Multicenter Study of the Italian Sarcoma Group

Abstract

The Italian Sarcoma Group performed this retrospective analysis of patients with advanced soft tissue sarcoma, pretreated with ≥1 anthracycline-based treatment, and treated with trabectedin every three weeks. Primary endpoint was to describe real-life use of trabectedin across Italy. Secondary endpoints included objective response rate (ORR) and safety. Overall, 512 patients from 20 Italian centers were evaluated. Leiomyosarcoma (37.7%)/liposarcoma (30.3%) were the most prevalent histological types (abbreviated as L-sarcoma). Patients received a median of four trabectedin cycles (range: 1–40), mostly as a second-line treatment (~60% of patients). The ORR was 13.7% superior (p < 0.0001) in patients with L-sarcoma compared with patients with non-L-sarcoma (16.6% vs. 9.0%). Median progression-free survival (PFS) was 5.1 months, whereas median overall survival (OS) was 21.6 months. Significantly better PFS and OS were observed in patients with L-sarcoma, those with objective responses and/or disease stabilization, treated in an early line and treated with reduced dose. Bone marrow toxicity (61.4%) and transaminase increases (21.9%) were the most common grade 3/4 adverse events. The results of this real-life study suggest that trabectedin is an active treatment, which is mostly given as a second-line treatment to patients with a good performance status and high-grade, metastatic L-sarcoma (clinical trial information: NCT02793050).

Analysis of clinical factors associated with survival in patients with soft-tissue sarcoma receiving trabectedin

“…Our results show a median PFS of 3.6 months for all patients, with a 4.2-month median for those with L-sarcoma and a 3.4-month median for those with non-L-sarcoma. These results are similar to the results of phase III trials [7,8] and the compassionate use program [17], although they are shorter than those of some more recent trials [15,16].…”

“…Most researchers who evaluated the influence of metastases on survival concluded that the metastatic pattern did not affect survival [15,17]. However, our research showed that the number of different metastatic sites as a surrogate marker of disease burden was the most significant factor affecting survival along with the tumor subtype.…”

“…Hence, evaluations of the effects of trabectedin on L-sarcomas as a single group without specifically analyzing for myxoid LPS might result in an inaccurate estimate of trabectedin effectiveness and may be at least partially responsible for the significant differences in PFS and OS between various studies [7,15]. Although Palmerini et al ., [15] suggested that additional STS types, such as synovial sarcoma, might derive benefit from trabectedin, we did not find any survival benefit for non-LPS STS. PFS tended to be longer for patients with LMS (hazard ratio, 0.41), synovial sarcoma (hazard ratio, 0.60) and undifferentiated pleomorphic sarcoma (hazard ratio, 0.72) compared to those with other sarcomas ( P > 0.05); however, while patients with LMS also tended to have longer OS (hazard ratio, 0.66), no such trend was recorded for patients with either synovial sarcoma (hazard ratio, 1.01) or undifferentiated pleomorphic sarcoma (hazard ratio, 1.33) ( P > 0.05).…”

Marine Power on Cancer: Drugs, Lead Compounds, and Mechanisms

“…A number of clinical phase I studies have found that it has a good effect on ovarian cancer when used alone or in combination with other chemotherapeutic drugs, such as cisplatin [ 68 , 69 , 70 ]. Phase II and III clinical studies have shown that trabectedin alone or in combination with other anticancer drugs is effective in soft tissue tumors, especially liposarcoma and leiomyosarcoma, and prolongs the survival time of the patients [ 30 , 71 , 72 , 73 ].…”

Inhibition of tumor‐associated macrophages by trabectedin improves the antitumor adaptive immunity in response to anti‐PD‐1 therapy

“…Trabectedin is a tetrahydroisoquinoline alkaloid that was originally extracted from a marine organism, the Tunicate Ecteinascidia turbinate , and is now synthetically produced by PharmaMar (Spain) [ 15 , 16 , 17 ]. Trabectedin, a registered antitumor agent, is used in the clinic for the second‐line treatment of soft tissue sarcoma, especially liposarcoma, and for relapsed platinum‐sensitive ovarian cancer patients, in combination with liposomal doxorubicin [ 18 , 19 , 20 , 21 , 22 ]. The mechanism of action of trabectedin on cancer cells is complex and different from that of other anticancer agents.…”