A pilot study of first-line olaratumab, doxorubicin and ifosfamide in patients with metastatic soft tissue sarcoma

e23531 Background: Standard treatment for patients with unresectable locally advanced or metastatic soft-tissue sarcoma is chemotherapy based on anthracyclines, while the tolerance of chemotherapy is limited. We assessed if anlotinib, a multitarget tyrosine kinase inhibitor, is efficacy and safety for the first-line treatment of these patients. Methods: This is an open-label, single-arm, multicenter, phase II clinical trial (NCT03792542) including 44 planned subjects. Eligible patients were aged 18-70 years old, diagnosed with locally advanced or metastatic soft-tissue sarcoma and had at least one measurable lesion according to RECIST 1.1. Other inclusion criteria included ECOG PS 0̃2, chemotherapy and anti-angiogenesis treatment naïve. Patients were administrated 12mg anlotinib once daily for 14 days every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Safety assessment was done in patients who received at least one dose of anlotinib. Here we report the results of a planned interim analysis. Results: From April 2019 to December 2020, 29 patients (16 males and 13 females) were enrolled from 7 hospitals in China. The median age is 57 (range 23-69). Pathological types included liposarcoma (n = 8), undifferentiated pleomorphic sarcoma (n = 5), fibrosarcoma (n = 5), synovial sarcoma (n = 4), and others (n = 7). At the data cutoff date on December 31, 2020, the median duration of treatment was 5.3 months, and the median PFS was not reached. 26 patients were eligible for the evaluation of tumor response.1 achieved partial response (PR) and the objective response rate (ORR) was 3.85% (1/26). 24 had stale disease (SD) and the disease control rate (DCR) was 96.2% (25/26). The clinical benefit rate (CBR), defined as the proportion of patients who achieved durable disease control (CR/PR/SD) more than 4 and 6 months, were 65.4% (17/26) and 38.5% (10/26) respectively. Most adverse events (AE) were grade 1 or 2. The most common grade 3 AE was hypertension (17.2%). No grade 4 AEs or treatment related death occurred in this study through the last follow-up. Conclusions: This interim analysis showed anlotinib of promising efficacy and favorable tolerance in the first-line treatment of locally advanced or metastatic soft- tissue sarcoma. Clinical trial information: NCT03792542.

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A phase 2 study using ipilimumab, nivolumab, and trabectedin for previously untreated metastatic soft tissue sarcoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.11562 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 11562-11562

Author(s):

Erlinda Maria Gordon ◽

Victoria S. Chua ◽

Ted T. Kim ◽

Neal Shiv Chawla ◽

Don Arlen Brigham ◽

...

Keyword(s):

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Phase 2 ◽

First Line ◽

Phase 2 Study ◽

Common Grade ◽

Metastatic Soft Tissue Sarcoma

11562 Background: Sarcoma cells are most immunogenic earlier in the disease course and before treatment when the immune system can recognize and destroy them. Hypothesis: Immune checkpoint inhibitors would be most effective when given to previously untreated patients with metastatic soft tissue sarcoma. Methods: Eligible patients for this Phase 2 study are previously untreated patients ≥ 18 years of age with unresectable or metastatic soft tissue sarcoma, with measurable disease by RECIST v1.1. Immune checkpoint inhibitors Ipilimumab (I) and Nivolumab (N) were given with Trabectedin (T), a marine derived alkaloid with defined doses of I (1 mg/kg i.v. q 12 weeks), N (3 mg/kg i.v. q 2 weeks), and T (1.2 mg/m2 i.v. q 3 weeks). Primary endpoints: (1) Objective response rate by RECIST v1.1 via CT scan or MRI, (2) Progression-free survival (PFS): from first day of treatment to disease progression or death due to any cause; otherwise, it is censored at the time of last follow-up, and (3) Overall survival: from first day of treatment to death due to any cause; otherwise, it is censored at the time of last follow-up. Results: There were eighty-two evaluable subjects, having completed the first cycle of I, N, and T and have had a CT or MRI scan at the 6-week follow-up period. Best Overall Response by RECIST v1.1 = 7 CR (2 surgical CR), 9 PR, 54 SD, and 12 PD. Disease control rate was 85.4%. The median PFS was >6.4 (range: 0-32) months; 6-month PFS rate: 57.3%. The median OS was >12.0 (0-38) months; 6-month OS rate: 78.8%. Safety analysis: The most common Grade 3 TRAEs include increased ALT (26), anemia (11), increased AST (9), and fatigue (8). Common Grade 4 TRAEs include thrombocytopenia (2), increased AST (2), increased ALT (2), and increased CPK (2). There was one Grade 5 TRAE of rhabdomyolysis (1). Conclusions: Taken together, these results suggest that first-line combinatorial therapy with I, N, and T are (1) synergistic, and (2) may be equal or superior to, and safer than, standard first line therapy for advanced/metastatic soft tissue sarcoma. Clinical trial information: NCT03138161.

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