Advanced alveolar soft part sarcoma responds to apatinib

Zhou, Yong; Tang, Fan; Wang, Yiying; Li, Min; Luo, Yi; Zhang, Wenli; Shi, Rui; Duan, Hong

doi:10.18632/oncotarget.18599

Cited by 23 publications

(25 citation statements)

References 48 publications

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“…Our collected data of toxicity (Table ) were differently distributed from what had already been described in clinical trials of apatinib . Our population was much younger than the participants in previous trials , which might influence the distribution of the side effects. Hypertension was not as severe in adolescents.…”

Section: Discussionmentioning

confidence: 92%

“…If a patient exhibited stable disease (SD), then the next evaluation would be performed 2 months later to confirm the SD and then repeated every 2 months thereafter. We strictly followed PR or progressive disease as described in RECIST 1.1 and did not set a minor response as performed by Grignani et al .…”

Section: Methodsmentioning

confidence: 99%

“…Previously, this drug was approved by regulatory authorities for the treatment of adenocarcinoma of the stomach or gastroesophageal junction . Besides, this agent has been used off‐label in the treatment of patients with advanced sarcoma throughout the country in the past 3 years, most of which have been proven to be effective, although with diverse response rates . To objectively assess its effectiveness and toxicity, we designed and conducted this prospective nonrandomized phase II trial to investigate the activity of apatinib in inoperable high‐grade osteosarcoma progressing upon chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial

et al. 2018

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Background Antiangiogenesis tyrosine kinase inhibitors (TKIs) have been shown to prolong progression‐free survival (PFS) in advanced osteosarcoma. Methylsulfonic apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor‐2. We aim to assess apatinib in patients with advanced high‐grade osteosarcoma progressing upon chemotherapy. Materials and Methods This phase II trial was conducted at Peking University People's Hospital. We enrolled participants (≥16 years of age) with progressive relapsed or unresectable osteosarcoma. Participants received 750 mg or 500 mg of apatinib according to body surface area once daily until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and PFS at 4 months. Results A total of 37 participants were finally included into the analysis. Until final follow‐up, the objective response rate (complete response + partial response) was 43.24% (16/37). The 4‐month PFS rate was 56.76% (95% confidence interval [CI], 39.43%–70.84%). Median PFS and overall survival were 4.50 (95% CI, 3.47–6.27) and 9.87 (95% CI 7.97–18.93) months, respectively. Toxic effects led to dose reductions or interruptions in a total of 25 of 37 (67.57%) patients. The most common grade 3–4 adverse events were pneumothorax in six (16.22%) patients, wound dehiscence in four (10.81%), proteinuria in three (8.11%), diarrhea in three (8.11%), and palmar‐plantar erythrodysesthesia syndrome in three (8.11%). No other serious adverse events were reported during the trial. There were no treatment‐related deaths. Conclusion Apatinib is a sensitive drug for advanced osteosarcoma with a high response rate after failure of chemotherapy, with similar duration of response compared to other TKIs. Implications for Practice For advanced osteosarcoma progressing upon chemotherapy, antiangiogenesis tyrosine kinase inhibitors (TKIs) have been proved to be effective in prolonging the progression‐free survival in previous multicenter trials and have been included into new National Comprehensive Cancer Network guidelines as second‐line therapy. Apatinib is a TKI that specifically inhibits vascular endothelial growth factor receptor‐2, which is domestically made in China. This phase II trial supports the use of apatinib in patients with advanced osteosarcoma progressing after chemotherapy.

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Section: Discussionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial

et al. 2018

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“…receiving apatinib. 10 Besides, Li et al reported the efficacy of apatinib at an initial dose of 500 mg in 10 stage IV sarcomas patients who received at least one complete cycle of treatment. 9 Among them, 2 patients achieved PR and 6 had SD; and an encouraging median PFS of 8.84 was detected.…”

Section: Discussionmentioning

confidence: 99%

“…Promising efficacy of apatinib was reported in several subtypes of sarcomas. [6][7][8][9][10] We further retrospectively investigated the outcomes of apatinib in 31 patients with advanced metastatic or recurrent sarcoma who pretreated with at least one chemotherapy regimen or refused to receive chemotherapy. in 7 patients (22.6%) and trunk in 3 patients (9.7%).…”

Section: Introductionmentioning

confidence: 99%

Efficacy and safety of apatinib monotherapy in advanced bone and soft tissue sarcoma: An observational study

Zhu

Xie

et al. 2018

Cancer Biology & Therapy

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Sarcomas are rare but malignant tumors with high risks of local recurrence and distant metastasis. Anti-angiogenic therapy is a potential strategy against un-controlled and not-organized tumor angiogenesis. We aimed to assess the safety and efficacy of apatinib, an oral tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, in patients with advanced sarcoma. Thirty-one patients who received initial apatinib between September 2015 and August 2016 were retrospectively reviewed. Among them, 19 (61.3%) patients were heavily pretreated with two or more lines of cytotoxic chemotherapy. Apatinib was given at a start-dose of 425 mg qd. During therapy, 9 (29.0%) patients required dose interruption and 7 (22.6%) needed dose reduction, and the mean dosage of apatinib was 372.9 ± 68.4 mg/day. In the study cohort, one patient was treated as adjunctive therapy and 6 patients stopped treatment before radiographic response assessment. Thus, 24 patients were eligible for tumor response evaluation. The objective response rate was 33.3% and clinical benefit rate was as high as 75.0%. The progression free survival was 4.25 (95% confidence interval [CI], 2.22-5.11) months, whereas the overall survival was 9.43 (95% CI, 6.64-18.72) months. Compared with other histological subtypes, leiomyosarcoma did not show significant survival benefits. Most of the adverse events (AEs) were at grade 1 or 2. The main grade 3 AEs were hypertension (6.5%), hand foot skin reaction (6.5%), and diarrhea (3.2%). In conclusion, apatinib showed promising efficacy and acceptable safety profile in metastatic or recurrent sarcoma, giving rationale clinical evidence to conduct clinical trials.

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Diagnosis, Prognosis, and Treatment of Alveolar Soft-Part Sarcoma

2019

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IMPORTANCE Alveolar soft-part sarcoma (ASPS) is a rare, translocation-driven sarcoma of the soft tissues. Alveolar soft-part sarcoma often affects young adults and is characterized by indolent behavior but early evidence of metastatic spread. After recognition of ASPS as a specific entity in 1952, retrospective data indicated prolonged survival in patients with metastases, despite inherent resistance to conventional doxorubicin-based chemotherapy. Tyrosine kinase inhibitors and immune checkpoint inhibitors have provided unexpected new treatment strategies for ASPS.OBSERVATIONS This review includes articles published between 1952 and March 1, 2018. With the introduction of new molecular diagnostic tools and therapies, the distinctive features of ASPS have become more evident. The identification and better understanding of molecular pathways activated by the characteristic t(X;17)(p11;q25) translocation and its correspondent chimeric ASPSCR1-transcription factor E3 (TFE3) fusion protein open new paths to drug development. The associations of TFE3 and facilitation of an immunosuppressive microenvironment provide a rationale for exploring treatments that affect the balance between T-effector cells and T-regulatory cells. Tyrosine kinase inhibitors, such as sunitinib, cediranib, and pazopanib, show activity with either tumor responses or disease stabilization in more than 50% of the cases. Given the association of new agents with patient outcomes, it is too early to say whether metastatic ASPS should still be considered incurable in all patients. CONCLUSIONS AND RELEVANCEThe biologic outcomes of the canonical genomic event in ASPS remain under investigation; a better understanding of the tumor microenvironment and the multiple pathways activated in this sarcoma, including unusual bioenergetics, MET signaling, and angiogenesis, should lead to more rational therapy. Basket trials and related prospective studies focusing on the intersection of specific signaling pathways and diseases with unique genomic features, such as ASPS, will provide an understanding of new options for care.

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Advanced alveolar soft part sarcoma responds to apatinib

Cited by 23 publications

References 48 publications

Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial

Apatinib for Advanced Osteosarcoma after Failure of Standard Multimodal Therapy: An Open Label Phase II Clinical Trial

Efficacy and safety of apatinib monotherapy in advanced bone and soft tissue sarcoma: An observational study

Diagnosis, Prognosis, and Treatment of Alveolar Soft-Part Sarcoma

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