Dataset Information

Efficacy and Safety of Anlotinib Combined with Liposomal Doxorubicin Followed by Anlotinib Maintenance in Metastatic Soft Tissue Sarcomas.

ABSTRACT:

Purpose

Anlotinib is a novel tyrosine kinase inhibitor with promising anti-tumor activity in patients with advanced soft tissue sarcomas (STS) in China. Liposomal doxorubicin monotherapy showed an encouraging effect on this disease. The aim of this study was to evaluate the efficacy and safety of anlotinib combined with liposomal doxorubicin followed by anlotinib maintenance in patients with metastatic STS.

Patients and methods

This is a multicenter, retrospective, observational study. We reviewed 27 patients with metastatic STS from July 2018 to December 2019, who were treated with anlotinib combined with liposomal doxorubicin followed by anlotinib maintenance in the absence of the tumor progression or intolerable adverse events (AEs).

Results

Of the 27 patients included, 2 patients had complete response (CR), 9 patients obtained partial response (PR), 11 patients achieved stable disease (SD). The objective response rate was 40.7%, the disease control rate was 81.5%, and the median progression-free survival (PFS) was 7 months (95% CI, 5.3-8.1 months). The progression-free rate (PFR) at 3 and 6 months was 81.5% and 59.3%, respectively. Most AEs were mild and acceptable. The most frequent grade 3/4 AEs were leukopenia (33.3%), febrile neutropenia (7.4%), and anemia (7.4%). No deaths related to the treatment were reported.

Conclusion

This study shows that anlotinib combined with liposomal doxorubicin followed by anlotinib maintenance is effective in patients with metastatic STS, and most AEs of this combined therapy are mild and acceptable. Further investigation on its efficacy is warranted.

SUBMITTER: Liu Z

PROVIDER: S-EPMC7871875 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and Safety of Anlotinib Combined with Liposomal Doxorubicin Followed by Anlotinib Maintenance in Metastatic Soft Tissue Sarcomas.

Liu Zhiyong Z Yao Weitao W Zhao Yao Y Liu Oufei O Zhang Peng P Ge Hong H

Cancer management and research 20210204

<h4>Purpose</h4>Anlotinib is a novel tyrosine kinase inhibitor with promising anti-tumor activity in patients with advanced soft tissue sarcomas (STS) in China. Liposomal doxorubicin monotherapy showed an encouraging effect on this disease. The aim of this study was to evaluate the efficacy and safety of anlotinib combined with liposomal doxorubicin followed by anlotinib maintenance in patients with metastatic STS.<h4>Patients and methods</h4>This is a multicenter, retrospective, observational s ...[more]

PMID: 33574700

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Project description:Background Conventional chemotherapy has limited therapeutic effects in retroperitoneal soft tissue sarcomas (RSTs), while anlotinib emerged as a novel multi-target tyrosine kinase inhibitor (TKI) for sarcomas. TKIs in combination with immunotherapy have demonstrated clinical activity in a variety of solid tumors. This study retrospectively analyzed the efficacy and safety of anlotinib plus camrelizumab for the treatment of RSTs. Methods Patients with RSTs who received anlotinib plus camrelizumab at Peking University Cancer Hospital Sarcoma Center were enrolled. Response assessment was conducted every 3 cycles of treatment according to response evaluation criteria in solid tumors version 1.1 (RECIST v1.1). Treatment-related adverse events (TRAEs) were evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Patients who had at least 1 response evaluation were analyzed. Results In all, 57 RSTs cases including 35 males and 22 females were analyzed, with a median age of 55 years. The pathological subtypes included 38 cases of L-sarcoma (liposarcoma and leiomyosarcoma), and 19 cases of non-L-sarcoma. Two patients (3.5%) had complete response (CR) and 13 patients (22.8%) had partial response (PR), with an objective response rate (ORR) of 26.3%. There were 31 (54.4%) and 11 (19.3%) patients with stable and progressive disease, respectively, with a disease control rate of 80.7%. Patients with non-L-sarcoma had a significantly better response rate than those with L-sarcoma (ORR: 52.6% vs. 13.2%; P=0.0031). After a median follow-up of 15.8 months, the median progression-free survival (PFS) was 9.1 months, with 3- and 6-month PFS rates of 83.6% and 60.8%, respectively. Patients with non-L-sarcoma had a significantly longer median PFS than did those with L-sarcoma (median PFS: 11.1 vs. 6.3 months; P=0.0256). TRAEs occurred in 28 (49.1%) patients, and 13 (22.8%) patients had grade 3–4 TRAEs. Hypertension (24.6%), hypothyroidism (19.3%), and palmar-plantar erythrodysesthesia syndrome (12.3%) were the most common TRAEs. Conclusions The combination of anlotinib and camrelizumab demonstrated possible therapeutic efficacy and safety in the treatment of RSTs, especially for non-L-sarcomas.

Project description:ImportanceActive therapeutic combinations, such as trabectedin and radiotherapy, offer potentially higher dimensional response in second-line treatment of advanced soft-tissue sarcomas. Dimensional response can be relevant both for symptom relief and for survival.ObjectiveTo assess the combined use of trabectedin and radiotherapy in treating patients with progressing metastatic soft-tissue sarcomas.Design, setting, and participantsPhase 1 of this nonrandomized clinical trial followed the classic 3 + 3 design, with planned radiotherapy at a fixed dose of 30 Gy (3 Gy/d for 10 days) and infusion of trabectedin at 1.3 mg/m2 as the starting dose, 1.5 mg/m2 as dose level +1, and 1.1 mg/m2 as dose level -1. Phase 2 followed the Simon optimal 2-stage design. Allowing for type I and II errors of 10%, treatment success was defined as an overall response rate of 35%. This study was conducted in 9 sarcoma referral centers in Spain, France, and Italy from April 13, 2015, to November 20, 2018. Adult patients with progressing metastatic soft-tissue sarcoma and having undergone at least 1 previous line of systemic therapy were enrolled. In phase 2, patients fitting inclusion criteria and receiving at least 1 cycle of trabectedin and the radiotherapy regimen constituted the per-protocol population; those receiving at least 1 cycle of trabectedin, the safety population.InterventionsTrabectedin was administered every 3 weeks in a 24-hour infusion. Radiotherapy was required to start within 1 hour after completion of the first trabectedin infusion (cycle 1, day 2).Main outcomes and measuresThe dose-limiting toxic effects of trabectedin (phase 1) and the overall response rate (phase 2) with use of trabectedin plus irradiation in metastatic soft-tissue sarcomas.ResultsEighteen patients (11 of whom were male) were enrolled in phase 1, and 27 other patients (14 of whom were female) were enrolled in phase 2. The median ages of those enrolled in phases 1 and 2 were 42 (range, 23-74) years and 51 (range, 27-73) years, respectively. In phase 1, dose-limiting toxic effects included grade 4 neutropenia lasting more than 5 days in 1 patient at the starting dose level and a grade 4 alanine aminotransferase level increase in 1 of 6 patients at the +1 dose level. In phase 2, among 25 patients with evaluable data, the overall response rate was 72% (95% CI, 53%-91%) for local assessment and 60% (95% CI, 39%-81%) for central assessment.Conclusions and relevanceThe findings of this study suggest that the recommended dose of trabectedin for use in combination with this irradiation regimen is 1.5 mg/m2. The trial met its primary end point, with a high overall response rate that indicates the potential of this combination therapy for achieving substantial tumor shrinkage beyond first-line systemic therapy in patients with metastatic, progressing soft-tissue sarcomas.Trial registrationClinicalTrials.gov Identifier: NCT02275286.

Project description:ObjectiveThe standard treatment for patients with advanced/metastatic soft tissue sarcomas (ASTS) is systemic chemotherapy with doxorubicin. A previous meta-analysis of 8 randomized controlled trials (RCTs) demonstrated the superiority of single-agent doxorubicin over doxorubicin-based combination chemotherapy for ASTS. However, meta-analyses of all RCTs that compare doxorubicin to other single-agent or combination regimens as first-line treatments for ASTS are lacking. We conducted a systematic review and meta-analysis to evaluate the efficacy and toxicity of current primary treatments for ASTS.MethodsEligible studies were RCTs of first-line chemotherapies for ASTS comparing doxorubicin alone to other single agents or to combination therapies (experimental arm). Data from studies reporting hazard ratios (HR) and 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS) were pooled. Other time-to-event endpoints were extracted from the studies based on Kaplan-Meier estimates, and pooled odds ratios (OR) and 95% CI were calculated.ResultsTwenty-seven eligible RCTs comprising 6156 patients were identified. Overall, the 1-year OS (OR 0.88, 95% CI 0.79-0.99, P = 0.03) was significantly improved in the experimental arm over the doxorubicin-only arm; however, there was no significant difference in 2-year OS (OR 0.87, 95% CI 0.73-1.03, P = 0.11) or OS (HR 0.97, 95% CI 0.91-1.03, P = 0.28) between the two groups. PFS and other time-to-event endpoints were not significantly different between the two treatment arms. While incidences of overall severe adverse events were not significantly different (OR 1.20, 95% CI 0.88-1.65, P = 0.26), severe nausea/vomiting was significantly more frequent in the experimental arm (OR 1.90, 95% CI 1.27-2.83, P = 0.002).ConclusionThe efficacies of doxorubicin-only and experimental arm regimens were similar, although toxicities were more frequent in the experimental arms. Hence, doxorubicin monotherapy remains suitable as a standard first-line regimen for ASTS.

Dataset Information

Efficacy and Safety of Anlotinib Combined with Liposomal Doxorubicin Followed by Anlotinib Maintenance in Metastatic Soft Tissue Sarcomas.

Purpose

Patients and methods

Results

Conclusion

Publications

Efficacy and Safety of Anlotinib Combined with Liposomal Doxorubicin Followed by Anlotinib Maintenance in Metastatic Soft Tissue Sarcomas.

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