Toxicity Of Apatinib Research Articles

The efficacy and safety of Apatinib in the treatment of advanced non-small cell lung cancer: A retrospective trial.

As a potent inhibitor of the vascular endothelial growth factor (VEGF) signaling pathway, Apatinib has been used in antitumor treatment for some time. The study aimed to research the therapeutic effects and toxicity of Apatinib in the treatment of advanced non-small cell lung cancer (NSCLC). We retrospectively analyzed 128 NSCLC patients treated with Apatinib in Qilu Hospital of Shandong University. Response Evaluation Criteria in Solid Tumors (RECIST) criteria was adopted to evaluate the treatment effect, and Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 was conducted to determine the Adverse Events (AEs). Cox proportional hazard model and Kaplan-Meier function were applied to evaluate the progression-free survival (PFS) and overall survival (OS). Among 128 NSCLC patients, partial response (PR) were observed in 15 patients, stable disease (SD) in 66 patients and progressive disease (PD) in 47 patients. The objective response rate (ORR) and disease control rate (DCR) accounted for 11.7% and 63.3% respectively. The median PFS (mPFS) and median OS (mOS) were 4.4 months and 17.2 months. Common side effects of Apatinib were hypertension (n=48), proteinuria (n=35), and hand-foot syndrome (HFS) (n=30), all of the side effects were controllable. No significant difference was observed in efficacy and AEs between the higher dose group (Apatinib>500mg/d) and the lower dose group (Apatinib=500mg/d). The study suggested that Apatinib with a lower dose (=500mg/d) has good efficacy and safety in the treatment of advanced NSCLC after first-line chemotherapy.

P64.03 A Phase II Single-Arm Trial of Apatinib as Maintenance Treatment Following First-Line Chemotherapy in Extensive Stage Small Cell Lung Cancer

For half a century, there is no breakthrough in maintenance therapy after first-line chemotherapy of extensive stage small cell lung cancer(ED-SCLC). Even though first-line chemotherapy combined with immunotherapy can prolong the overall survival(OS) of ED-SCLC patients, the benefit is not satisfactory. The disease often progresses rapidly, and the therapy after the first-line treatment is very limited. The development of therapy to delay cancer progression and prolong survival after initial chemotherapy for SCLC is an unmet clinical need. Recently, small, orally administered multi-target TKIs , such as apatinib, have exerted promising effects on SCLC. This study enrolled 12 ED-SCLC patients to study the efficacy and toxicity of apatinib in maintenance therapy after standard first-line chemotherapy. The primary endpoints were OS and progression-free survival (PFS). The secondary endpoints included toxicity and safety. Apatinib was given 250 mg/day during the chemotherapy interval, and as maintenance therapy after 4–6 cycles until the patient progressed, died, or was intolerant to drug toxicity. The patients who received apatinib as maintenance treatment exhibited a median PFS of 3.7 months (range=1.3–6.2). The median OS was 16.3 months (range=9.7-22.8). Two patients required dose reduction due to adverse effects. The most common AEs included hypertension (n = 4,33.33%) and hand-foot-skin reaction (n = 2, 16.67%). One patient developed diarrhea and one patient developed hemoptysis. The most serious side effect was intestinalobstruction As a maintenance treatment after first-line chemotherapy , apatinib not only showed anti-tumor activity for further tumor shrinkage, but also had the potential to prolong OS in ED-SCLC and would be a potent therapeutic option in future clinical practice.

Efficacy and safety of apatinib in treatment of gastric cancer: A real-world study.

182 Background: Apatinib is a small molecule TKI inhibitor, which had been approved in China for treatment of advanced gastric cancer refractory to two or more lines of prior chemotherapy. Its efficacy and safety have been demonstrated in previous randomized controlled clinical studies. However, the efficacy and safety of apatinib in real world is lacking. This study aimed to evaluate the anti-tumor activity and toxicity of apatinib in real world. Methods: Patients older than 18 years with histologically diagnosed with gastric cancer were enrolled and treated with either apatinib alone or in combination with other drugs. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), overall response rate (ORR) and disease control rate (DCR). The adverse events were also recorded. Results: From March 2018 to March 2019, a total of 1000 patients were enrolled. Among them, 48(0.48%), 13(0.13%), 225 (22.5%), 389 (38.9%), and 325 (32.5%) patients received apatinib as postoperative auxiliary-, neoadjuvant-, first-, second-, and third- or higher line therapy, respectively. Efficacy evaluation was performed in 901 patients. Thirty-five patients achieved complete response (CR), 116 patients achieved partial response (PR), 596 patients achieved stable disease (SD), and 154 patients had progressive disease (PD), illustrating an ORR of 16.76% and a DCR of 82.91%. The mPFS was 5.32 months (95% CI, 4.93-5.75), and mOS was 9.76 months (95% CI, 8.97-10.81). In addition, the mOS of apatinib in first-line, second-line, and third-line treatments were 12.68 months, 9.49 months, and 7.62 months, respectively. Patients received apatinib in combination with other drugs had longer survival than apatinib alone, with mPFS 5.62 months vs 4.47 months and mOS 10.81 months vs 7.95 months. Such phenomenon was also observed in ORR (18.21% vs 13.04%, P< 0.001) and DCR (84.88% vs 77.87%, P< 0.001). The main adverse events (AE) were anemia (67.2%), thrombocytopenia (36.2%), leukopenia (34.5%)and anorexia (37.6%). The most common grade 3-4 adverse events included neutropenia, anemia and thrombocytopenia. Conclusions: In the real world, apatinib showed promising efficacy and manageable toxicities in patients with gastric cancer. Patients benefit more when received apatinib combination therapy. Clinical trial information: NCT03478943.

Efficacy and Safety of Apatinib Treatment for Patients with Advanced Intrahepatic Cholangiocarcinoma.

PurposeEffective treatment options for intrahepatic cholangiocarcinoma (ICC) are limited. This study was intended to explore the efficacy and safety of apatinib in advanced ICC with lymph node metastasis or distant metastasis.Patients and MethodsThe efficacy and toxicity of apatinib were evaluated in patients with ICC between November 2017 and March 2020 at the Second Affiliated Hospital of Anhui Medical University. Survival analysis was estimated using Kaplan–Meier method.ResultsTen patients with advanced ICC were enrolled. The median progression-free survival (PFS) was 3.0 months (95% CI: 1.450–4.550). No patient achieved a complete response (CR). One patient gained partial response (PR), and 6 patients had stable disease (SD). The objective response rate (ORR) was 10%, and the disease control rate (DCR) was 70%. The common treatment-related adverse events were hypertension (20%), proteinuria (30%), hand and foot syndrome (10%) or emesis (10%). No grade 3/4 toxicities occurred. Toxicities were mild and tolerable.ConclusionApatinib is potentially an effective treatment option with tolerable toxicities for patients with advanced ICC.

Apatinib as first-line treatment in patients with advanced hepatocellular carcinoma: a phase II clinical trial.

BackgroundThe 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.MethodsThis 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.ResultsBetween 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%).ConclusionsApatinib showed robust clinical activity in patients with advanced HCC. Moreover, apatinib was safe to use, well tolerated, and had acceptable toxicity. (NCT03046979).

Application of apatinib after multifaceted therapies for metastatic breast cancer.

BackgroundApatinib is a small molecule tyrosine kinase inhibitor (TKI) that is taken orally and has high specificity for vascular endothelial growth factor receptor 2 (VEGFR-2). This study explored the efficacy and toxicity of apatinib in patients with metastatic breast cancer (MBC) who failed to respond to multifaceted therapy.MethodsA total of 61 patients with MBC who were unresponsive to previous multifaceted chemotherapy were included in this study. The treatment regimens were either a combination of apatinib and chemotherapy or apatinib administered singly with a dose range of 250 mg every second day to 500 mg per day. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and toxicity were used as outcome measures.ResultsOf the 61 patients, partial response (PR) was observed in 14 patients (23.0%), stable disease (SD) was observed in 30 patients (49.2%), and progressive disease (PD) was observed in 17 patients (27.8%). The DCR was 44/61 (72.1%), and the ORR was 14/61 (23.0%). Of the 44 patients who achieved PR or SD, the median PFS was 4 months and 15 days. Patients with intracranial metastases were found to benefit from apatinib. Furthermore, 11 patients underwent next generation sequencing (NGS) and 5 of these had a P53 mutation. Of those 5 cases, the ORR and DCR were 0% and 20.0%, respectively. Of the 6 cases with wild-type P53, the ORR was 50.0%, and the DCR was 100.0%. Multivariate regression analysis found that hypertension was an independent prognostic factor of better DCR.ConclusionsApatinib showed good efficacy and manageable toxicity in patients with MBC that had not responded to multifaceted therapy.

A randomized phase 2 trial of apatinib vs observation as maintenance treatment following first\xadline induction chemotherapy in extensive\xad stage small cell lung cancer

SummaryBackground The 5-year survival rate for extensive-disease small-cell lung carcinoma (ED-SCLC) is only 1%. Recently, apatinib exerted promising effects on cancer patients after failure of first-line chemotherapy. Methods This study enrolled 24 ED-SCLC patients to study the efficacy and toxicity of apatinib in combination with chemotherapy and maintenance therapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included toxicity and safety. Apatinib was given 250 mg/day during the chemotherapy interval, and as maintenance therapy after 4–6 cycles until the patient progressed, died, or was intolerant to drug toxicity. The study further evaluated the cytotoxicity, cell-cycle arrest and apoptotic induction of apatinib in A549 and H446 cells. Results There was no difference in short-term efficacy between combined and chemotherapy groups. Long-term efficacy showed that the median PFS was 7.8 months and 4.9 months in combination and chemotherapy groups, respectively [p = 0.002, HR(95%CI): 0.18(0.06–0.60)]. The median OS was 12.1 months and 8.2 months in combination and chemotherapy groups, respectively [p = 0.023, HR(95%CI): 0.38 (0.16–0.90)]. Multivariate Cox regression analysis showed that apatinib combined with chemotherapy was an independent prognostic factor for OS and PFS. The ECOG score was an independent prognostic factor affecting OS. In vitro analysis showed that apatinib inhibited cell proliferation and caused cell-cycle arrest and apoptosis. Conclusion Apatinib combination/maintenance therapy showed promising efficacy and safety to extend OS/PFS in ED-SCLC and will be a potent therapeutic option in future practice. Although the scale of this study is small, further research on large sample sizes is needed.

The efficacy and safety of anlotinib treatment for advanced lung cancer.

ObjectiveAnlotinib is an oral novel multi-target tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, and stem cell factor receptor (c-Kit). The aim of this study was to evaluate the efficacy and safety of anlotinib treatment in advanced lung cancer in the real world.MethodsWe evaluated the efficacy and toxicity of apatinib in patients with previously treated advanced lung cancer from 2018 to 2019 in Zhejiang Cancer Hospital. Survival analysis was performed by the Kaplan–Meier method.ResultsFifty-eight patients were included in the present study. Thirty-one of these patients received anlotinib treatment as a third line and 27 patients received further therapy. All 58 patients had therapeutic evaluation and 46 patients acquired progression-free survival evaluation. Ten patients achieved partial response (PR), and 36 achieved stable disease (SD), representing a response rate of 17.2% and a disease control rate of 77.6%. Median progression-free survival was 3.3 months (95% CI 1.595–5.071). The toxicities associated with anlotinib were generally acceptable with a total grade 3/4 toxicity of 5.2%. The toxicities of anlotinib were generally tolerated and the common toxicities were hand–foot syndrome and hypertension.ConclusionIn the third-line or more-line treatment of advanced lung cancer, anlotinib appears to have some activity when utilized as a salvage treatment. Adverse reactions are controllable.

A retrospective six-patient series of apatinib for the treatment of persistent or recurrent carcinoma of the cervix.

ObjectiveAlthough advances have been made in the clinical and therapeutic management of women with cervical cancer, the best treatment for patients with metastatic or recurrent cervical cancer is still undefined. Apatinib, a novel inhibitor of vascular endothelial growth factor receptor-2 tyrosine kinases, has been successful in treating various malignancies. This study was conducted to evaluate the efficacy and safety of apatinib in the treatment of recurrent cervical cancer.MethodsPatients with recurrent cervical cancer received apatinib after failure of the second- or higher-line chemotherapy. Apatinib was administered as 500 mg daily on days 1 through 21 of each 4-week cycle. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events were reviewed and evaluated.ResultsSix patients were administered apatinib for at least one complete cycle. The median OS was 16.0 months (95% CI: 6.8–25.2), and the median PFS was 7.0 months (95% CI: 2.2–11.8), One patient achieved partial response and three patients achieved stable disease. Two patients were evaluated as progression disease. The ORR was 16.7% (1/6) and the DCR was 67.7% (4/6). The common side effect of apatinib was hypertension; however, the toxicity of apatinib was tolerable and controllable.ConclusionsApatinib is an option in the treatment of recurrent cervical cancer after failure of the second- or higher-line chemotherapy. Further prospective evaluation of the utility of apatinib is required.

Clinical investigation of the efficacy and toxicity of apatinib (YN968D1) in stage III/IV non-small cell lung cancer after second-line chemotherapy treatment: A retrospective study.

BackgroundThis study was designed to assess the clinical efficacy and toxicity of apatinib (YN968D1) as third or subsequent‐line treatment for stage III/IV non‐small cell lung cancer (NSCLC).MethodsA total of 100 patients with advanced NSCLC who were treated with apatinib at a daily dose of 250/425/500 mg at Shandong Cancer Hospital from January 2016 to June 2018 were enrolled in our study. The objective response, disease control, and median progression‐free survival rates were reviewed and evaluated. Univariate and multivariate analyses were performed to determine the prognostic factors. The main adverse events were evaluated per the Common Terminology Criteria for Adverse Events version 4.0.ResultsAll patients were assessable for response. No complete responses were observed, 11 patients achieved a partial response, and 56 showed stable disease. The objective response rate was 11.0%, the disease control rate was 67.0%, and the median progression‐free survival was 2.93 months (95% confidence interval 2.07–3.87). In Cox regression analysis, the Eastern Cooperative Oncology Group performance status score (hazard ratio 1.799; P < 0.05) and smoking history (hazard ratio 1.958; P < 0.05) were predictive indicators for apatinib treatment efficacy. Treatment‐related adverse events were tolerated, predictable, reversible, and controllable.ConclusionApatinib was found to be both effective and safe in advanced NSCLC patients without a genetic driver mutation who experienced progression after two or more lines of chemotherapy treatment.

Efficacy and safety of apatinib in patients with advanced nonsmall cell lung cancer that failed prior chemotherapy or EGFR-TKIs: A pooled analysis.

Background:Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor-2. A weighted pooled analysis was performed to evaluate the clinical outcome, efficacy, and toxicity of apatinib in patients with advanced nonsmall cell lung cancer (NSCLC) that failed prior treatment with chemotherapy or epidermal growth factor receptor-TKIs (EGFR-TKIs).Methods:The literature published in PubMed, Embase, and Cochrane Library databases was searched (from inception to November 30, 2017) for eligible trials using the following search terms: apatinib AND (lung cancer OR NSCLC). Meeting abstracts were also reviewed to identify appropriate studies. Inclusion criteria were as follows: prospective or retrospective studies that evaluated efficacy and/or safety of apatinib in patients with advanced NSCLC that failed prior chemotherapy or EGFR-TKIs; primary outcome included one of these endpoints, progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), or adverse events (AEs); English language; and number of cases in the study ≥10 cases.Results:A total of 457 patients with advanced NSCLC were treated with apatinib in 14 studies (10 retrospective and 4 prospective studies) and were included in this pooled analysis. The pooled median PFS was 4.77 months [95% confidence interval (CI), 4.11–5.00] in all groups, 4.80 months (95% CI, 4.65–4.95) in the 750 mg apatinib (high-dose) group, and 3.88 months (95% CI, 3.11–4.65) in the 250 to 500 mg apatinib (low-dose) group. Median PFS stratified by single apatinib therapy or apatinib combined with continuous EGFR-TKIs was 4.76 months (95% CI, 3.66–5.06) and 5.20 months (95% CI, 3.66–6.74), respectively. The pooled median OS, ORR, and DCR values were 6.85 months, 18%, and 72%, respectively; pooled median ORR and DCR were 15% and 72% in the 750 mg apatinib group versus 20% and 72% in the 250 to 500 mg apatinib group. ORR and DCR stratified by therapeutic regimens were 14% and 70% for single-agent apatinib, 29% and 88% for apatinib combined with continuous EGFR-TKIs, and 26% and 63% for apatinib combined with chemotherapy, respectively. The pooled AE rates of grade 3/4 were hypertension (7%), proteinuria (3%), hand-foot-skin reaction (6%), fatigue (4%), decreased appetite (1.1%), oral mucositis (3%), and thrombocytopenia (3%).Conclusion:Apatinib has promising antitumor activity and manageable toxicity profile in patients with advanced NSCLC that failed prior chemotherapy or EGFR-TKIs. This result needs to be confirmed through the ongoing Phase III clinical trial.

PUB008 Successful Treatment with Apatinib plus Human Endostatin for Refractory Recurrent Advanced Pulmonary Carcinosarcoma: A Case Report

Primary pulmonary carcinosarcoma composed of a mixture of carcinoma and sarcoma elements is exceedingly rare. Advanced pulmonary carcinosarcoma is associated with a poor prognosis. This study aimed to review the efficacy and safety of Apatinib combined with recombinant human endostatin in patients with advanced pulmonary carcinosarcoma who failed in the second-line chemotherapy. A 53-year-old male was diagnosed with recurrent pulmonary carcinosarcoma and failed in the prior chemotherapy (including first-line chemotherapy: epirubicin plus ifosfamide, and second-line chemotherapy: gemcitabine plus cisplatin). The patient was treated with oral apatinib and intravenous injection human endostatin. Apatinib was administered at a dose of 500mg/d P.O, while continuous intravenous pump of 30mg/d human endostatin was given for 7 days, with 4 weeks in a cycle. The patient achieved partial response evaluated by Chest computerized tomography (CT) after 4 weeks medication and had an progression-free-survival of 24 weeks. The common side effects related to treatment was hand-foot syndrome and hypertension; however, the toxicity of apatinib plus human endostatin was controllable and tolerable. The preliminary results of this case indicate that apatinib plus human endostatin has outstanding efficacy for refractory primary pulmonary carcinosarcoma, but this still warrants further investigation.

Apatinib monotherapy for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.

e20626 Background: Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), has been proved to be effective and safe in treating patients with advanced gastric cancer who failed to second-line chemotherapy. As the VEGFR-2 targeted therapy has made encouraging progress in the treatment of a broad range of malignancies, we aimed to explore the efficacy and safety of apatinib in treatment of advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Methods: In this open-label single-arm, phase II study, patients were treated with apatinib alone in daily dose of 250 mg, po, in the second- or third-line setting. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Results: From January 28, 2016 to December 31, 2016, 33 patients were enrolled, including 9 patients with squamous carcinoma and 24 patients with adenocarcinoma. Fourteen patients were detected as EGFR mutations and all the cases have no anaplastic lymphoma kinase (ALK) fusion gene. The median progression free survival (mPFS) of the whole group was 4.0 (95% confidence interval [CI], 0-8.2) months, while the mPFS of adenocarcinoma was 4.0 (95% CI, 2.1-5.9) months and the mPFS of squamous carcinoma was 5.5 (95% CI, 0-13.9) months (P = 0.245). Among the 33 patients, partial response was noted in 3 patients (9.09 %) and stable disease in 14 (42.42%). The disease control rate (DCR) was 51.52%. The common side effects of apatinib were hypertension, hand-foot syndrome and proteinuria, which accounted for 33.33%, 24.24%, and 15.15%, and no grade 3/4 adverse reactions occurred. The toxicity of apatinib was controllable and tolerable. Conclusions: Apatinib appears to be effective and safe for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Prospective studies are needed for further investigation.

Salvage treatment with apatinib for advanced non-small-cell lung cancer

ObjectiveNo definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second- or third-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, in advanced NSCLC as salvage treatment.MethodsWe evaluated the efficacy and toxicity of apatinib in patients with previously treated advanced NSCLC from 2014 to 2015 in Zhejiang Cancer Hospital. Survival analysis was performed by the Kaplan–Meier method.ResultsForty-two patients were included in the present study. Four patients achieved partial response, and 22 achieved stable disease, representing a response rate of 9.5% and a disease control rate of 61.9%. Median progression-free survival and overall survival were 4.2 and 6.0 months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%.ConclusionApatinib appears to have some activity against advanced NSCLC when utilized as salvage treatment.