scholarly journals A Retrospective Analysis of the Efficacy and Safety of Anlotinib in the Treatment of Advanced Sarcoma

Author(s):  
Qiang Yan ◽  
Xinhui Du ◽  
Liangyu Guo ◽  
Weitao Yao

Abstract Background: Patients with advanced sarcomas have a dismal prognosis with few effective therapies. Previous research has demonstrated the efficacy of anlotinib in the treatment of advanced sarcomas. However, there are few relevant clinical studies, and the efficacy of anlotinib varies among sarcomas of different subtypes. Therefore, more clinical studies are needed to explore the efficacy of anlotinib in different subtypes of sarcomas. This study assessed the efficacy and safety of anlotinib monotherapy in the treatment of advanced sarcoma. Methods: Data from 45 advanced sarcoma patients who received anlotinib monotherapy at Affiliated Cancer Hospital of Zhengzhou University between June 2018 and February 2021 were retrospectively analyzed, including 5 cases of osteosarcoma and 40 cases of soft tissue sarcoma(STS). According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1, we evaluated objective response rates (ORR) and disease control rates (DCR) at 3 months, as well as overall ORR and DCR, and calculated progression-free survival(PFS), and then evaluated treatment-related adverse events (AEs). Results: 44 patients were evaluated for efficacy and 45 for treatment-related AES. The ORR and DCR after 3 months were 6.82% and 81.82% respectively. At the end of follow-up, the overall ORR was 2.27%, the total DCR was 27.27%, and the median progression-free survival (m-PFS) was 5.71 months. Among them, the m-PFS of alveolar soft tissue sarcoma (ASPS) was 8.07 months, which was significantly longer than that of other subtypes of sarcoma (P=0.025). The most common adverse events were hypothyroidism (increased TSH) (17.8%), anemia (15.6%), fatigue (11.1%), loss of appetite (11.1%), decreased liver function (11.1%), leukopenia (8.9%) and hand-foot syndrome (8.9%). After treatment, 5 patients developed grade 3 AES, including decreased liver function (4.4%), hypertension (2.2%), proteinuria (2.2%), fatigue (2.2%), and loss of appetite (2.2%). One patient had severe myelosuppression and a significant decrease in white blood cells and platelets. It is worth noting that the PFS of patients with hand-foot syndrome after treatment was significantly longer than that of patients without hand-foot syndrome (P < 0.05). Conclusion: Anlotinib is effective in the treatment of sarcoma, especially in ASPS, Synovial sarcoma (SS) and Fibrosarcoma (FS), and its toxicity is controllable. In addition, the occurrence of hand-foot syndrome after treatment may be related to a good prognosis. However, large sample and prospective studies are needed to confirm it.

2020 ◽  
Vol 48 (7) ◽  
pp. 030006052092640
Author(s):  
Guan-Li Su ◽  
Yuan-Yuan Wang ◽  
Jin-Cheng Wang ◽  
Hao Liu

Objective We performed this meta-analysis to compare the efficacy and toxicity of regorafenib and TAS-102. Methods Electronic databases were searched to identify studies comparing the efficacy and safety of regorafenib and TAS-102 in patients with chemotherapy-refractory metastatic colorectal cancer using pooled analyses. Results Three clinical trials were included in this analysis. Regarding the reasons for treatment discontinuation, regorafenib was significantly associated with disease progression (odds ratio [OR] = 0.33, 95% confidence interval [CI] = 0.21–0.50) and adverse events (OR = 4.38, 95% CI = 2.69–7.13). However, overall (OR = 0.97, 95% CI = 0.81–1.17) and progression-free survival (OR = 1.01, 95% CI = 0.86–1.18) did not significantly differ between the groups. The most common treatment-related adverse events in the regorafenib group were neutropenia (OR = 0.06, 95% CI = 0.03–0.11), hand–foot syndrome (OR = 50.34, 95% CI = 10.44–242.84), and liver dysfunction (OR = 34.51, 95% CI = 8.30–143.43). Conversely, the incidence of thrombocytopenia did not differ between the two groups. Conclusions Regorafenib and TAS-102 have similar efficacy but different adverse event profiles. Differences in the toxicity profiles of the two drugs will help guide treatment selection.


2021 ◽  
pp. JCO.21.00124
Author(s):  
Anne-Sophie Defachelles ◽  
Emilie Bogart ◽  
Michela Casanova ◽  
Johannes H. M. Merks ◽  
Gianni Bisogno ◽  
...  

PURPOSE The VIT-0910 trial was conducted to evaluate efficacy and safety of the vincristine-irinotecan combination with and without temozolomide (VIT and VI, respectively) in relapsed or refractory rhabdomyosarcoma (RMS). METHODS In this randomized European phase II trial, patients age 0.5-50 years received 21-day cycles combining vincristine (1.5 mg/m2 once a day on day 1 and day 8) and irinotecan (50 mg/m2 once a day from day 1 to day 5) with and without temozolomide (125 mg/m2 once a day from day 1 to day 5 and 150 mg/m2 once a day from cycle 2), until progression or unacceptable toxicity. The primary end point was objective response rate after two cycles. Secondary end points included best response, progression-free survival, overall survival, and adverse events. A Simon 2-stage design was initially planned to separately analyze 40 patients/arm. After amendment, the trial sample size was increased to 120 and a comparison between arms, adjusted for confounding factors, was added to the statistical plan (ClinicalTrials.gov, NCT01355445 ). RESULTS Overall, 120 patients (60 per arm) were recruited in 37 European centers. The median age was 11 years (range, 0.75-45); 89% of patients had a relapsed RMS. The objective response rate was 44% (24 of 55 evaluable patients) for VIT versus 31% (18 of 58) for VI (adjusted odds ratio, 0.50; 95% CI, 0.22 to 1.12; P = .09). The VIT arm achieved significantly better overall survival (adjusted hazard ratio, 0.55; 95% CI, 0.35 to 0.84; P = .006) compared with VI, with consistent progression-free survival results (adj-hazard ratio, 0.68; 95% CI, 0.46 to 1.01; P = .059). Overall, patients experienced adverse events ≥ grade 3 more frequently with VIT than VI (98% v 78%, respectively; P = .009), including a significant excess of hematologic toxicity (81% v 61%; P = .025). CONCLUSION The addition of temozolomide to VI improved chemotherapy efficacy for patients with relapsed RMS, with manageable increase in toxicity. VIT is considered the new standard treatment in these patients in the European paediatric Soft Tissue Sarcoma Group and will be the control arm in the next randomized trial.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e23530-e23530
Author(s):  
Xin Sun ◽  
Wei Guo ◽  
Ranxin Zhang ◽  
Lu Xie ◽  
Jie Xu

e23530 Background: Anthracycline-based chemotherapy is the main first-line treatment option for advanced soft-tissue sarcoma (STS). Anlotinib has been approved for the treatment of STS by the Chinese agency. This study was performed to evaluate the efficacy and safety of Anlotinib combined with liposomal doxorubicin in first-line treatment of patients with advanced STS. Methods: This is a single-center, retrospective study. Eligible patients were those ≥14 years old, ECOG performance state of 0-1, with histologically confirmed locally advanced, unresectable or metastatic STS, previously untreated, with measurable disease by RECIST v1.1. All patients received Anlotinib (12mg once daily, 2 weeks on and 1 week off) and liposomal doxorubicin (40-50 mg/m2, IV, D1, every 3 weeks) until disease progression or unacceptable adverse events. The primary endpoint was progression-free survival (PFS). Disease control rate (DCR), objective response rate (ORR), and side effects were also calculated. Results: Between April 2019 and December 2020, 8 patients were evaluated, including 2 undifferentiated pleomorphic sarcoma, 1 liposarcoma, 4 fibrosarcomas, and 1 synovial sarcoma. The median age was 42 years. 2 patients (25%) achieved a confirmed partial response (PR) and 3(37.5%) had stable disease (SD). The ORR and DCR were 25% and 62.5% respectively. The median PFS was 11.3 months, and the PFS rate at 4 months was 50%. Treatment-related adverse events included hand-foot syndrome (3/8, 37.5%), pneumothorax (1/8, 12.5%), oral mucositis (2/8, 25%), epistaxis (2/8, 25%), hypertension (2/8, 25%), arrhythmias (1/8, 12.5%), and pharyngeal pain (1/8, 12.5%). Three patients experienced grade 3 or 4 adverse events, 2 hand-foot syndrome (2/8, 25%) and 1 pneumothorax (1/8, 12.5%). Conclusions: This study suggested that the combination of Anlotinib and liposomal doxorubicin might have anti-tumor activity and acceptable toxicity in first-line treatment of patients with advanced STS.


2020 ◽  
Vol 38 (5) ◽  
pp. 1559-1569 ◽  
Author(s):  
Zhichao Tian ◽  
Huimin Liu ◽  
Fan Zhang ◽  
Liangyu Li ◽  
Xinhui Du ◽  
...  

Summary Background Previous studies have demonstrated the efficacy of apatinib and anlotinib for the treatment of sarcomas. However, more clinical data and evidence are needed to support clinical treatment selection and study design. Here, we evaluated the effectiveness and safety of these two drugs for the treatment of sarcomas. Methods We retrospectively reviewed the data of 110 patients with advanced osteosarcoma (n = 32) or soft tissue sarcoma (STS, n = 78) who received oral apatinib or anlotinib therapy during May 2016–February 2019 at two centers. Patients were divided into the apatinib and anlotinib groups. Results Among osteosarcoma patients, the objective response rates (ORRs) for the apatinib and anlotinib groups were 15.79% (3/19) and 7.69% (1/13), respectively. The disease control rates (DCRs) were 63.16% (12/19) and 30.77% (4/13), and the median progression-free survival (m-PFS) was 4.67 ± 3.01 and 2.67 ± 1.60 months, respectively. Among STS patients, ORRs for the apatinib and anlotinib groups were 12.24% (6/49) and 13.79% (4/29), respectively. The DCRs were 59.18% (29/49) and 55.17% (16/29), and m-PFS was 7.82 ± 6.90 and 6.03 ± 4.50 months, respectively. Regarding adverse events (AEs), apatinib was associated with a higher incidence of hair hypopigmentation and pneumothorax, while anlotinib was associated with a higher incidence of pharyngalgia or hoarseness. Conclusion Both apatinib and anlotinib were effective for the treatment of sarcomas. However, the effectiveness of the two drugs and associated AEs varied based on the histological type of sarcoma. These differences may be due to their different sensitivities to targets such as RET, warranting further study.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 11547-11547
Author(s):  
Jiayong Liu ◽  
Zhengfu Fan ◽  
Wei Guo ◽  
Tian Gao ◽  
Shu Li ◽  
...  

11547 Background: Anlotinib, a multitargeted tyrosine kinase inhibitor, had been prove to be effective for the treatment of advanced or metastatic soft tissue sarcoma(STS) faild anthracycline chemotherapy. With the lack of prospective data of combination of PDL-1 inhibitor and antiangiogenic agent, we designed a phase 1b study to investigated the efficacy and safety of anlotinib plus TQB2450 in patients with STS. Methods: Eligible patients (age 18-70, ECOG 0-1, with histopathologically confirmed advanced STS, at least one measurable lesion according to RECIST 1.1, and previously received front-line anthracycline chemotherapy) were included and received anlotinib (12mg qd, D1-14, 21d/cycle) plus TQB2450 (1200 mg, IV, D1, 21d/cycle) until disease progression or intolerable toxicities.The primary endpoint was objective response rate (ORR), secondary endpoints included safety, overall survival (OS), progression-free survival (PFS), disease control rate (DCR). Results: From January 2019 to January 2021, 30 pts were enrolled1, 12 alveolar soft part sarcoma and 18 others (7 synovial sarcoma, 4 leiomyosarcoma, 5 undifferentiated pleomorphic sarcoma, 1 fibrosarcoma and 1 epithelioid sarcoma). ORR by RECIST was 36.7%, DCR was 83.3%, 11/30 pts had PR, 14/30 (46.7%) had SD, 5/30 (16.7%) PD. Median PFS was 9.6 m in all pts and 4.9m. in non-ASPS, respectively. Median OS in non-ASPS was 10.27m, while mOS in all pts and both mPFS and mOS in ASPS had not been reached. Notably, to ASPS pts, ORR was 75%, and DCR was 100%. The most common 1-2 grade treatment-related adverse reaction (TRAE) was hypothyroidism (19/30,63.3%),hypercholesterolemia (16/30, 53.3%) and hypertriglyceridemia (16/30, 53.3%), the most common ≥3 grade TRAEs were hypertriglyceridemia (3/30, 10%). 6 SAE (20%) occurred, including 2 pneumothorax, 1 Immune associated hapatic injury, 1 hypotension, 1 Immune myocarditis and 1 diabetic ketoacidosis. Conclusions: The combination of anlotinib and TQB2450 showed promising activity in second-line treatment of advanced STS, especially in ASPS, with well tolerance and acceptable toxicity.


2020 ◽  
Author(s):  
Xiaoyao Feng ◽  
Jing Li ◽  
Aomei Li ◽  
Han Zhou ◽  
Xixu Zhu ◽  
...  

Abstract BackgroundSoft tissue sarcoma(STS) is a malignant tumor of highly heterogeneous mesenchymal origin. STS has a biologic pattern and clinical transformation with localized invasive growth and susceptibility to hematogenous metastasis. Metastatic and recurrent soft tissue sarcoma may be treated by local therapeutic options, including surgery and radiation therapy. This study evaluated the safety and efficacy of SBRT for metastatic and recurrent soft tissue sarcoma.MethodsWe performed a retrospective analysis of 37 STS patients with 58 lesions treated with SBRT from 2009-2019 at our institution. We analyze the local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates of the patients.ResultThe median follow-up was 20 months(range 2 to 120 months). One and two year LC rates were 75.3% and 55.2% [95% confidence interval (CI) 20–25 months]. Median OS was 24 months and the survival rates were 66.6%, 45% and 26.6% at 1, 2 and 3-year after SBRT. Median PFS were 11months (95% CI 8–18 months). No acute or chronic grade ≥ 3 toxicity was observed.ConclusionsIn patients with metastatic and recurrent STS, LC, OS and PFS were higher than expected. SBRT should be a proper treatment option for STS.


2005 ◽  
Vol 23 (3) ◽  
pp. 576-584 ◽  
Author(s):  
A. Le Cesne ◽  
J.Y. Blay ◽  
I. Judson ◽  
A. Van Oosterom ◽  
J. Verweij ◽  
...  

Purpose This nonrandomized multicenter phase II study was performed to evaluate the activity and safety of Ecteinascidin (ET-743) administered at a dose of 1.5 mg/m2 as a 24-hour continuous infusion every 3 weeks in patients with pretreated advanced soft tissue sarcoma. Patients and Methods Patients with documented progressive advanced soft tissue sarcoma received ET-743 as second- or third-line chemotherapy. Antitumor activity was evaluated every 6 weeks until progression, excessive toxicity, or patient refusal. Results One hundred four patients from eight European institutions were included in the study (March 1999 to November 2000). A total of 410 cycles were administered in 99 assessable patients. Toxicity mainly involved reversible grade 3 to 4 asymptomatic elevation of transaminases in 40% of patients, and grade 3 to 4 neutropenia was observed in 52% of patients. There were eight partial responses (PR; objective regression rate, 8%), 45 no change (NC; > 6 months in 26% of patients), and 39 progressive disease. A progression arrest rate (PR + NC) of 56% was observed in leiomyosarcoma and 61% in synovialosarcoma. The median duration of the time to progression was 105 days, and the 6-month progression-free survival was 29%. The median duration of survival was 9.2 months. Conclusion ET-743 seems to be a promising active agent in advanced soft tissue sarcoma, with no cumulative toxicities. The 6-months progression-free survival observed in advanced soft tissue sarcoma compares favorably with those obtained with other active drugs tested in second-line chemotherapy in previous European Organisation for the Research and Treatment of Cancer trials. The median overall survival was unusually long in these heavily pretreated patients mainly due to the high number of patients who benefit from the drug in terms of tumor control.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shenghao Wu ◽  
Cuiping Zheng ◽  
Songyan Chen ◽  
Xiaoping Cai ◽  
Yuejian Shi ◽  
...  

Objective. To investigate the efficacy and safety of the treatment of the newly diagnosed multiple myeloma (MM) patients with the therapy of subcutaneous (subQ) administration of bortezomib and dexamethasone plus thalidomide (VTD) regimen.Methods. A total of 60 newly diagnosed MM patients were analyzed. 30 patients received improved VTD regimen (improved VTD group) with the subQ injection of bortezomib and the other 30 patients received conventional VTD regimen (VTD group).The efficacy and safety of two groups were analyzed retrospectively.Results. The overall remission (OR) after eight cycles of treatment was 73.3% in the VTD group and 76.7% in the improved VTD group (P>0.05). No significant differences in time to 1-year estimate of overall survival (72% versus 75%,P=0.848) and progression-free survival (median 22 months versus 25 months;P=0.725) between two groups. The main toxicities related to therapy were leukopenia, neutropenia, thrombocytopenia, asthenia, fatigue, and renal and urinary disorders. Grade 3 and higher adverse events were significantly less common in the improved VTD group (50%) than VTD group (80%,P=0.015).Conclusions. The improved VTD regimen by changing bortezomib from intravenous administration to subcutaneous injection has noninferior efficacy to standard VTD regimen, with an improved safety profile and reduced adverse events.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 696-696 ◽  
Author(s):  
Andres Negro-Vilar ◽  
Zofia Dziewanowska ◽  
Eric Groves ◽  
Elyane Lombardy ◽  
Victor Stevens

Abstract Denileukin diftitox (ONTAK®) is a genetically engineered fusion protein composed of the enzymatically active domain of diphtheria toxin and the full length sequence of interleukin-2 (IL-2), designed to target malignancies expressing the IL-2 receptor. The drug is approved for the treatment of CTCL in patients expressing the CD-25 component of the IL-2 receptor. L4389-14 is a phase III study designed to further evaluate the efficacy and safety of denileukin diftitox (DD) in distinct subgroups of CTCL patients. The study met its accrual goal of 90 patients and included three subgroups of patients: 1) CD25 (+) patients that crossover from a placebo course of treatment in a companion study (L4389-11) and had progressed or failed to respond during an 8-course placebo treatment (N=34); 2) CD25 (−) patients (N=36) and 3) CD25 (+) patients that had previously been treated with DD, responded, and subsequently relapsed (retreatment group, N=22). Patients entered the study at stages Ia to III and received DD at a dose schedule of 18mcg/Kg/day by IV infusion once daily for 5 days every 3 weeks for up to 8 cycles. Efficacy of treatment was assessed based on tumor burden, lymph nodes, lymphocyte count, and patient status (PGA) at every cycle, beginning on cycle 2. A response assessment required confirmation in two subsequent cycles. Responses were evaluated by an independent Drug Evaluation Review Committee. Assessment of activity of DD across the 3 groups based on an analysis of the data is shown in the table below. Patient demographics were consistent across subgroups and representative of a general CTCL population. Disease status at baseline was Stage IIa or earlier 66% of patients and stage IIb or higher 34% of patients. About 46% of patients presented with mild to severe erythroderma. Adverse events were similar to those previously observed with ONTAK. Serious adverse events of ≥5% incidence were nausea (9%), vomiting (5%), capillary leak syndrome (5%), pyrexia (9%) and infections (10%). The results of this large phase III trial showed very consistent efficacy of denileukin diftitox across treatment-naïve CD25 (+) and CD25 (−) patients, as well as in patients undergoing retreatment with DD. Duration of response and progression free survival were also quite favorable across the different CTCL subgroups. Response Assessment CD25 (+) Placebo Crossover CD25 (−) CD25 (+) Retreatment N = 34 36 22 ORR (CR/CCR/PR) 47.1% 30.6% 36.4% CR/CCR 17.6% 8.3% 9.1% PR 29.4% 22.2% 27.3% SD 29.4% 44.4% 31.8% PD 20.6% 25.0% 31.8% Duration of Response (days) 820 340 274 Progression Free Survival (days) 870 Not reached 429


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