Clinical study of apatinib in the treatment of stage IV osteogenic sarcoma after failure of chemotherapy.
ABSTRACT: Objective: To analyze the efficacy and safety of apatinib in the treatment of stage IV osteogenic sarcoma after chemotherapy failure through a single-arm, prospective, and open clinical phase II study. Methods: Information on 34 patients with stage IV osteogenic sarcoma treated with apatinib after failure of chemotherapy in Tianjin Medical University Cancer Institute and Hospital between September 2015 and December 2019 was collected and analyzed. The participants included 23 males and 11 females, with an average age of 35.24 years (11-73 years). The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), PFS rate (PFR), and overall survival (OS) were evaluated. The treatment-related adverse events (AEs) and safety of apatinib were also evaluated. Results: Of the 34 patients, 33 were able to be evaluated for efficacy. One patient received apatinib treatment for less than one cycle; therefore, only safety analysis was performed. The 12-week clinical evaluation showed that 2 patients had a partial response (PR), 24 patients had stable disease (SD), and 7 patients had progressive disease (PD). The ORR, DCR, and PFR at 12 weeks were 6.06% (2/33), 78.79% (26/33), and 82%, respectively. By the end of the follow-up, 6 patients had SD (18.18%, 6/33), 27 patients had PD (81.82%, 27/33), and 15 patients died because of disease progression (45.45%, 15/33). The ORR was 0 (0/33), the DCR was 18.18% (6/33), and the median PFS (mPFS) was 7.89 months (95% CI: 4.56-11.21). The median OS (mOS) was 17.61 months (95% CI: 10.85-24.37). The most common treatment-related AEs were hand-foot syndrome (35.29%, 12/34), proteinuria (32.35%, 11/34), and hypertension (32.35%, 11/34). Conclusions: Apatinib is effective and well tolerated in stage IV osteogenic sarcoma patients after chemotherapy failure.
Project description:Apatinib (YN968D1) is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). We conducted a single-arm, nonrandomized phase II study (NCT03121846) to assess the efficacy and safety of apatinib in patients with stage IV sarcoma. We recruited 64 patients with stage IV sarcoma who had failed chemotherapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were progression-free survival rate (PFR), objective response rate (ORR), and disease control rate (DCR) at week 12. Treatment-related adverse effects (AEs) were evaluated. Fifty-nine patients were assessed for efficacy and 64 patients for AEs. The median PFS was 7.93 months. At 12 weeks, the PFR was 74%, the ORR was 16.95% (10/59), and the DCR was 86.44% (51/59). The final ORR was 15.25% (9/59) and the DCR was 57.63% (34/59). Notably, 22 patients (34.38%) who developed hypertension, hand-foot-skin reaction, or proteinuria had significantly longer OS than those without these AEs (18.20 vs. 10.73 months; P?=?0.002). We conclude that apatinib is effective and well tolerated in patients with advanced sarcoma. The development of hypertension, hand-foot-skin reaction, or proteinuria may indicate a favorable prognosis, representing a novel finding in sarcoma patients.
Project description:Angiogenesis inhibitors are of considerable interest for treating metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of apatinib in chemotherapy-refractory mCRC. Apatinib 500?mg was administered daily to patients who had progressed after two or more lines of standard fluorouracil-based chemotherapy. Primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and toxicity. Overall, 48 patients were enrolled. ORR and DCR were 8.3% (4/48) and 68.8% (33/48), respectively. Median PFS and OS were 4.8 (95% confidence interval [CI], 3.653-5.887) and 9.1 months (95% CI, 5.155-13.045), respectively, and did not differ between subgroups stratified by previous anti-angiogenic therapies. The most prevalent grade 3-4 adverse events were hypertension (12.5%), hand-foot syndrome (HFS, 10.4%), thrombocytopenia (10.4%), and proteinuria (8.3%). Low baseline neutrophil/lymphocyte ratio (NLR, hazard ratios [HR], 0.619; P?=?0.027), early carbohydrate antigen 19-9 (CA19-9) decrease (HR, 1.654; P?=?0.016), and HFS (HR, 2.087; P?=?0.007) were associated with improved PFS. In conclusion, apatinib monotherapy demonstrated encouraging efficacy with manageable toxicities in chemotherapy-refractory mCRC. Previous anti-angiogenic therapies did not influence outcomes. Baseline NLR, early CA19-9 decrease, and HFS could predict the efficacy of apatinib.
Project description:Background:Apatinib, a selective inhibitor of vascular endothelial growth factor receptor 2 (VEGFR 2), has exhibited modest antitumor efficacy in hepatocellular carcinoma (HCC). We aimed to evaluate the effectiveness and tolerability of apatinib versus sorafenib in patients with advanced HCC. Methods:All patients with advanced HCC who underwent sorafenib or apatinib between January 2016 to December 2017 were retrospectively reviewed. Seventy-two patients received apatinib (26 patients, 500 mg, daily) or sorafenib (46 patients, 400 mg, twice daily) until disease progression or intolerable toxicities. Primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), objective response rate (ORR) per modified response evaluation criteria in solid tumors (RECIST), disease control rate (DCR), and safety. Results:The median follow-up was 13.2 (5.7-20.7) months. The 1-year OS for apatinib of 62.0% was comparable to that of sorafenib [64.2%, hazard ratio (HR), 1.15; 95% confidence interval (CI), 0.369-3.58]. The median PFS was 4.1 months in the apatinib group (95% CI, 3.2 to 7.4 months) and 3.6 months in the sorafenib group (95% CI, 2.7 to 5.9 months; HR, 1.03; 95% CI, 0.586 to 1.800; P=0.925). The apatinib group exhibited higher ORR (19.2% vs. 2.2%, P=0.012) but similar DCR (57.7% vs. 50%, P=0.530) compared with the sorafenib group. The most common any-grade adverse events in the apatinib and sorafenib groups were hand and foot syndrome (53.8% vs. 50%), hypertension (50% vs. 19.6%), diarrhea (34.6% vs. 28.3%), and elevated transaminase (57.7% vs. 63%). Conclusions:Compared with sorafenib, apatinib yielded comparable PFS and OS, and even better ORR, in patients with advanced HCC.
Project description:Background:The prognosis for advanced hepatocellular carcinoma (HCC) remains clinically unsatisfying. Apatinib has proven to be a very effective treatment for advanced HCC in our previous retrospective study. Our aim in this study was to evaluate the efficacy, safety, and toxicity of apatinib in patients with advanced HCC. Methods:This single-arm, open-label phase II clinical trial enrolled patients with advanced HCC. These patients received apatinib, 500 mg once daily, until disease progression, unacceptable toxicity, consent withdrawal, or death. One treatment cycle consisted of 4 weeks of apatinib treatment. The response evaluation criteria in solid tumors (RECIST) was used to assess tumor response every 1-2 cycles. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were the overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and toxicity. Results:Between December 2016 and June 2018, 23 patients were enrolled in the study, 22 of whom were available for response evaluation. The cutoff date was August 10, 2018. The overall ORR and DCR were 30.4% and 65.2%, respectively. The median OS and PFS were 13.8 (95% CI: 5.3-22.3) and 8.7 (95% CI: 5.9-11.1) months, respectively. The most common treatment-related adverse events were proteinuria (39.1%), hypertension (34.8%), and hand-foot-skin reaction (34.8%). Conclusions:Apatinib showed robust clinical activity in patients with advanced HCC. Moreover, apatinib was safe to use, well tolerated, and had acceptable toxicity. (NCT03046979).
Project description:<h4>Background</h4>Alpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting.<h4>Methods</h4>From September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer, were enrolled to perform this analysis. Patients received oral apatinib as monotherapy or combination therapy. A treatment cycle was defined as 28 days. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcomes included safety, objective response rate (ORR), and disease control rate (DCR).<h4>Results</h4>Twenty patients were evaluated for the apatinib efficacy analysis. The ORR of apatinib was 10%, whereas the DCR was 70%. The median PFS was 3.5 months [95%confidence interval (CI): 2.34-4.66]. The median OS was 4.5 months (95%CI: 3.49-5.51). Median OS of AFPGC patients without carcinoembryonic antigen (CEA) elevation achieved 30.8 months. CEA elevation was considered to be a potential independent predictive factor for OS (P?=?0.030) and PFS (P?=?0.047) by the analysis of multivariate analysis. The most common grade 3 to 4 adverse events (AEs) were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%).<h4>Conclusion</h4>Apatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC as a rare sub-type of gastric cancer.<h4>Trial registration</h4>AHEAD-G202 (NCT02668380).
Project description:Currently, patients with radioiodine refractory differentiated thyroid cancer (RAIR-DTC) have limited treatment options. In this study, we aimed to assess the short-term efficacy and safety of apatinib in RAIR-DTC. Ten adult patients were prospectively enrolled to receive oral apatinib (750 mg q.d). The primary endpoints were change in serum thyroglobulin (Tg) concentration, disease control rate (DCR) and objective response rate (ORR) based on RECIST 1.1 criteria. The secondary endpoints included change in glucose metabolism, evaluated by maximum standard uptake value (SUVmax), and safety. As early as 2 weeks after apatinib treatment, the serum Tg concentration decreased by 21.0% in 8 patients available for detection without interference, and a further sharp decline by 81.4% compared with the baseline level occurred at 8 weeks post-treatment. The DCR and ORR were 100% (10/10) and 90% (9/10), respectively. The sum of tumor diameter shrank to 22.8±8.1 mm from 38.8±15.7 mm (P=0.001). Moreover, a significant decrease in SUVmax was observed from 6.53±5.14 to 2.56±1.67 and 2.45±1.48 at 4-week and 8-week time-points after treatment (P=0.032 and 0.020), respectively. The common grade 3 adverse events (AEs) included hand-foot-skin reaction (50%), hypertension (30%), and hypocalcemia (20%). No severe AE related to apatinib was observed during treatment. Hence, apatinib seems to be a promising therapeutic option for RAIR-DTC patients. Apart from RECIST 1.1 criteria, the biochemical marker (Tg) and glucose metabolism index (SUVmax) could be adopted in assessing the early response to TKI in RAIR-DTC.
Project description:Background and purpose:Apatinib is a novel, oral, small-molecule tyrosine kinase inhibitor that targets VEGFR-2. Recent clinical trials have revealed its broad-spectrum anticancer effect. However, most recent studies of apatinib have involved single-arm studies with insufficient cases, different doses of drugs, and different incidences of adverse events (AEs), which has resulted in a lack of accurate measurement of the efficacy and safety of apatinib. Thus, we performed this meta-analysis to evaluate the efficacy and safety of apatinib. Methods:In total, 21 studies from five databases (PubMed, ScienceDirect, ClinicalTrials.gov, China National Knowledge Infrastructure [CNKI], and Cochrane Library) were included in this meta-analysis. All statistical analyses in this meta-analysis were performed using Stata 14.0 software. We used objective response rate (ORR) and disease control rate (DCR) to evaluate the efficacy of apatinib for five major types of solid tumors. Additionally, we used the total incidence of AEs and the incidence of the three most common grade 3-4 AEs to evaluate the safety of apatinib. Results:The pooled results for the efficacy of apatinib in the treatment of different types of solid tumors revealed that patients treated with apatinib exhibited good disease control. In addition, it was likely that an increased dose of apatinib resulted in an increased ORR in lung and breast cancer and an increased DCR in liver and gastric cancer. Although AEs appeared in 84% of patients included in this meta-analysis, most of these AEs were of grades 1-2 and were well tolerated and controlled. The most common grade 3-4 AEs included hypertension, hand-foot syndrome, and proteinuria. Importantly, there were no significant differences in these grade 3-4 AEs with higher doses of apatinib. Conclusion:Apatinib is a novel VEGFR-2 inhibitor with proven efficacy and safety for solid tumors. The meta-analysis reveals the broad-spectrum anticancer effect of apatinib.
Project description:BACKGROUND:Apatinib is an oral small-molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Some clinical trials have demonstrated that apatinib is efficacious against advanced nonsquamous NSCLC. OBJECTIVE:This study aimed to probe efficacy and safety of apatinib plus docetaxel, as the second or above line treatment, in advanced nonsquamous NSCLC. DESIGN:Multicenter, prospective, single arm study. SETTING:Three teaching hospitals centers in the Sichuan. PARTICIPANTS:Fourteen patients with stage IVA/B nonsquamous NSCLC had previously received at least 1 platinum-based chemotherapy regimen. INTERVENTION:Patients who were enrolled between November 2016 and January 2018 were given docetaxel (75?mg/m, i.v., d1) plus oral apatinib (250?mg/d), 4 weeks as one cycle, until disease progression or intolerance to adverse events (AE). MAIN OUTCOME MEASURES:The primary endpoint was progression-free survival (PFS). The secondary endpoints comprised objective response rate (ORR), disease control rate (DCR), overall survival (OS), and AE incidence rate. RESULTS:All patients carried adenocarcinoma by pathological type. The median follow-up duration was 9.76 months. Out of 14 cases, 12 were evaluable, showing ORR of 33.33%, DCR of 66.67%, DCR of 50% in cases with brain metastasis, median PFS of 2.92 months (95% CI: 1.38-4.48), and 6-month OS of 80%. Primary AEs encompassed: leukopenia in 7 cases (58.33%), hand-foot skin reaction in 5 cases (41.67%), and diarrhea in 4 cases (33.33%). Among them, grade 3 AEs were: leukopenia in 4 cases (33.33%), and hand-foot skin reaction in 1 case (8.33%). No grade 4/5 AEs were reported. Univariate and multivariate analysis were conducted respectively for PFS and OS. These factors encompassed: gender, age, gene mutations, clinical stage, ECOG scores, quantity of metastatic foci, brain metastasis, and hand-foot skin reaction. Results demonstrated zero risk factors for PFS or OS. CONCLUSION:Apatinib plus docetaxel, as the second or above line treatment, is effective and safe against advanced nonsquamous NSCLC, with good tolerance profile. TRIAL REGISTRATION:NCT03416231.
Project description:<h4>Introduction</h4>We performed this clinical trial to evaluate the efficacy and safety of apatinib and oral etoposide in patients with HER2-negative locally advanced or metastatic breast cancer (MBC).<h4>Methods</h4>Patients with HER2-negative MBC previously treated with anthracycline and taxanes and failed ?1 prior chemotherapy regimens were recruited. The starting dose of apatinib was 500 and 425 mg in patients with ECOG scores of 0-1 and 2, respectively. The etoposide capsules were given at 50 mg/m<sup>2</sup> on days 1 to 10 for 21 days. The primary end point was objective response rate (ORR). Secondary end points included progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety.<h4>Results</h4>Thirty-one eligible patients were enrolled. The median follow-up time was 11 months. The median PFS for all patients was 6.9 months [95% confidence interval (CI) 6.0-7.9], and 6.9 months (95% CI 5.3-8.6) and 6.6 months (95% CI 1.4-11.7) for patients with apatinib 425 and 500mg once daily, respectively. The ORR was 35.5% (11/31). The DCR was 87.1% (27/31). The median OS was 20.4 months (95% CI 11.4-29.3). The median PFS of patients who had hypertension and proteinuria was longer than that for those without hypertension and proteinuria. The most common grade 3/4 treatment-related AEs were hypertension (12/31, 38.7%), fatigue (3/31, 9.7%), thrombocytopenia (3/31, 9.7%).<h4>Conclusion</h4>Apatinib combined with etoposide capsules is effective and tolerable in heavily pretreated, metastatic HER2-negative breast cancer patients. A lower apatinib dose provide equivalent efficacy and reduced toxicity.<h4>Clinical trial registration</h4>https://clinicaltrials.gov/, identifier NCT03535961.
Project description:Objective:This study aimed to determine the efficacy and tolerability of apatinib plus dose-dense temozolomide (TMZ) as first-line treatment for recurrent glioblastoma (rGBM). Methods:Patients with rGBM were enrolled in this study. Patients were subjected to concurrent treatment of apatinib (500 mg qd) and dose-dense TMZ (100 mg/m2, 7 days on with 7 days off) until disease progression or intolerable toxicity. Efficacy was evaluated using Response Assessment in Neuro-Oncology criteria for high-grade glioma. Safety was assessed using NCI-CTCAE 4.0. Survival was estimated with Kaplan-Meier curve and log rank test. Results:From March 2016 to January 2018, 20 eligible patients who had relapsed from the standard chemoradiotherapy regimen (TMZ and radiotherapy) were enrolled in this study. The median follow-up time was 12 months. All patients were eligible for efficacy analysis. The objective response rate (ORR) was 45%. The disease control rate (DCR) was 90%. The median progress-free survival time was 6 months (95% CI, 5.3 to 7.8 months). The 6-month progression-free survival rate was 50%. The median overall survival was 9 months (95% CI, 8.2 to 12.2 months). The most common treatment-related adverse events were hypertension (21%), hand-foot syndrome (16%), leukopenia (14%), and thrombocytopenia (12%). Conclusion:Apatinib combined with dose-dense TMZ was effective in terms of PFS, ORR, and DCR and was well tolerated after appropriate dose reduction in the Chinese population tested. Further randomized controlled clinical studies are needed to confirm the efficacy of apatinib combined with TMZ for treatment of rGBM.