Apatinib In Patients Research Articles

A phase II study of apatinib treatment for advanced biliary tract carcinoma after failure of the standard chemotherapy.

e16684 Background: There is no standard second-line therapy for advanced biliary tract carcinoma (BTC). Apatinib, a VEGFR2 tyrosine kynase inhibitor, showed an inhibitary effect on tumor formation in BTC tumorgraft mouse model in previous study, with tolerable toxicity in clinical trials for other types of advanced cancer such as gastric cancer. We conducted an exploratory study to evaluate the efficacy and safety of apatinib in patients with advanced BTC. Methods: This is a single-center, single-arm phase II study (NCT03427242). The key inclusion criteria were:(1) histologically confirmed advanced or metastatic BTC; (2) Prior lack of response or intolerance to at least one chemotherapeutic regimens; (3) At least one measurable lesion as defined by RECIST 1.1; (4) No prior use of anti-angiogenic targeted drugs. Eligible patients received oral apatinib 500mg each day continuously until unacceptable toxicity or tumor progression. The primary endpoint was progression free survival (PFS). The secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment safety. Results: From Dec 1, 2017 to Jan 31, 2020, a total of 18 patients (12 males and 6 females) had been recruited, and 16 patients who had received the medication of apatinib were included in this analysis. Among these patients, 10 were previously treated with only first-line chemotherapy and 6 were treated with two or more lines of therapy. The median age was 65 (range 45-76) years old. Fourteen patients had received the efficacy evaluation after treatment. Two patients achieved partial response (PR, 14.3%), 6 patients with stable disease (SD, 42.9%),and 6 patients with progressive disease(PD). The ORR and DCR were 14.3% and 57.1%, respectively. At the last follow-up date on Jan 30, 2020, 4 patients are still on apatinib medication. The median PFS was 2.70 months (95% CI, 1.94 - 3.46), and the median OS was 7.03 months (95% CI, 3.16 - 10.9). Grade 3 or 4 adverse events were reported in 7 patients (43.8%). The detailed grade 3 or 4 adverse events were proteinuria in 5 patients, hand-foot syndrome in 2 patients, platelet count decrease in 1 patients, diarrhea in 1 patients and urine bilirubin in 1 patients (Table). Conclusions: For the patients with advanced biliary tract carcinoma, apatinib showed an anti-tumor activity with acceptable safety. Clinical trial information: NCT03427242 . [Table: see text]

Apatinib to prolong overall survival from recurrence to death in metastatic breast cancer: A single-center experience from east China.

e13090 Background: To observe the efficacy and side effects of apatinib in patients with metastatic breast cancer in non-clinical trial setting. Methods: Patients with metastatic breast cancer who were treated in Zhejiang Cancer Hospital from January 2014 to September 2019 were collected from the hospital information system. According to whether patients were treated with apatinib, they were divided into apatinib group and control group. There were significant differences in baseline data such as the age of onset between the two groups, and the propensity score match was used to ensure balance. The survival time from the first recurrence to death was compared between the two groups. The progression-free survival, the incidence of side effects and the types of side effects of apatinib were observed. The prognostic factors of apatinib were also analyzed. Results: There were 297 patients who met the criteria, of whom 40 received apatinib treatment. After propensity score match, the balance of the two groups was guaranteed. Compared with the control group, the hazard ratio of apatinib group was 0.111 from first recurrence to death (95% confidence interval: 0.022 to 0.556, p = 0.007). The median progression-free survival of apatinib was 8 months. Patients often received apatinib at the end of the disease. And 67.5% (27/40) of patients received apatinib at the end line. 52.5% (21/40) of patients had adverse reactions, and common adverse reactions included myelosuppression (7/40), fatigue (6/40), hypertension (6/40), proteinuria (5/40), skin and mucosal reactions (5/40) and so on. Three of them had grade Ⅲ to Ⅳ adverse reactions, including hypertension, myelosuppression and skin ulceration. Severe adverse reactions increased the risk of progression-free survival with apatinib. Its hazard ratio is 10.103 (95% confidence interval: 1.149 to 88.825, p = 0.037). Conclusions: As the choice of multi-line therapy for metastatic breast cancer, apatinib can prolong the survival time after recurrence. The adverse reactions are common, so it is necessary to guard against the severe adverse reactions that lead to poor prognosis.

Camrelizumab plus apatinib in patients with advanced cervical cancer: A multicenter, open-label, single-arm, phase II trial.

6021 Background: Camrelizumab is a fully humanized, monoclonal antibody against PD-1. We aimed to assess the efficacy and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor targeting VEGFR2, in patients with advanced cervical cancer. Methods: In this open-label, single-arm, phase 2 study done at four centres in China, eligible patients were aged 18–70 years, had an ECOG performance status of 0 or 1, progressed after at least one line of systemic chemotherapy for metastatic, recurrent or persistent cervical cancer, and had measurable disease. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once daily. Treatment continued until disease progression, unacceptable toxicity, and withdrawal of consent. The primary endpoint was the objective response rate (ORR) assessed by RECIST version 1.1. An optimal Simon two-stage design was employed to test the null hypothesis of a 17% ORR versus 35% alternative (1-sided alpha 0.10, 80% power), if > 3 responses out of the first 16 patients were observed, then the study would continue to enroll a total of 44 patients. Results: Between Jan 21st, 2019, and Aug 1st, 2019, 45 patients were enrolled and received study treatment (safety population). The median age was 51 (range, 33–67) years. Median previous treatment lines were 2 (range, 1–4). As of Jan 22, 2020, median follow-up was 9.2 months (range, 2.4–12.2). 25 (59.5%; 95%: CI 44.7–74.4) of 42 patients who had at least one post-baseline tumor assessment (efficacy evaluable population) achieved an objective response, including two (4.8%) complete response, and 23 (54.8%) partial response. Median duration of response was not reached. The disease control rate was 88.1% (37/42). Median progression-free survival (PFS) was 7.6 months (95% CI: 5.8–not reached). 31 (68.9%) patients had grade ≥ 3 treatment-related adverse events (TRAEs). Grade ≥ 3 TRAEs occurring in ≥ 5% of patients were hypertension (24.4%), anemia (20.0%), fatigue (15.6%), γ-glutamyltransferase increased (13.3%), neutropenia (6.7%), and thrombocytopenia (6.7%). In post-hoc analyses, objective response was noted in 20 (69%) of 29 patients with PD-L1-positive tumors, and in 5 (50.0%) of 10 patients with PD-L1-negative tumors (Chi-square test, P = 0.281). PFS was longer in patients with PD-L1-positive tumors than patients with PD-L1-negative tumors (median PFS: 9.6 versus 5.3 months; log-rank test, P = 0.017). Conclusions: Camrelizumab plus apatinib showed promising antitumor activity and tolerable toxicities in patients with advanced cervical cancer. Clinical trial information: NCT03816553.

A phase II open-label, multicenter, study to evaluate the efficacy and safety of rivoceranib in subjects with recurrent or metastatic adenoid cystic carcinoma.

TPS6597 Background: Adenoid cystic carcinoma (ACC) is a rare salivary gland malignancy, also found in other secretory gland sites (tracheobronchial tree, esophagus, breast, lungs, prostate, uterine cervix and vulva). Initial disease is typically treated with surgical resection and radiation, but recurrent or metastatic disease remain to be a significant challenge. There is no standard systemic therapy option for advanced ACC, although recent studies with tyrosine kinase inhibitors have shown moderate objective response and disease stabilization rates. Rivoceranib (also known as apatinib) is a potent selective inhibitor of VEGFR-2 and has been evaluated in a single arm phase II study of 59 recurrent or metastatic ACC patients in China and has demonstrated an (ORR) of 47.1% and disease control rate of 98.1. Methods: This is a phase II, open-label, multicenter[HGJ3], single arm clinical trial of oral rivoceranib (700 mg daily) in patients with recurrent or metastatic ACC of any anatomic site, not amenable to curative surgery or radiotherapy to confirm activity of rivoceranib. Subjects must have at least one evaluable lesion by RECIST v1.1 and have evidence of disease progression within the 6 months prior to study entry. Fifty-five subjects will be enrolled at 7 US sites and 4 South Korean sites. The primary endpoint is ORR assessed by investigators with a target ORR of 25% to detect a difference of 15% from the historical ORR of 10% at 1-year (this achieves 80% power with a 5% significance level). Secondary endpoints include overall survival, disease control rate, progression free survival at 6, 12 and 24 months and time to progression. Exploratory objectives include correlation between ORR and the presence of MYB/MYB-L1 fusion, pharmacokinetics evaluation, and patient-reported quality of life assessments by FACT-G. This study is open and enrolling at the time of submission.

Real-world observation of the efficacy and prognostic factors analysis of apatinib for patients with advanced gastric cancer.

e15508 Background: Apatinib is the first oral anti-angiogenic agent approved for the treatment of advanced gastric cancer in China. With the development of marketing promotion, the real world observation of the efficacy and prognostic factors analysis of apatinib become the urgent need for clinical decision. The aim of this study is to evaluate the efficacy and safety of apatinib in patients with advanced gastric cancer, and the association between some prognostic factors and clinical outcomes. Methods: We collected the data of 153 patients with advanced gastric cancer, who were treated with apatinib after failure of at least one regimen chemotherapy from December 2014 to June 2019. Treatment response, progression-free survival(PFS), overall survival(OS) and treatment-related adverse events were evaluated. Results: The median PFS for 153 patients was 3.1m (95% confidence interval, CI 2.863-3.337). The median OS was 6.0m (95% CI 4.392-7.608). Adverse events of grade 3 or above happened in 47.6 percent of patients and 61.7 percent of whom stopped treatment. Multivariate analysis showed that the number of metastatic sites was the independent factor simultaneously predicting DCR (disease control rate, P = 0.008) and OS (P = 0.007). Patients spending more than one year from diagnosis to treatment with apatinib had better DCR (P = 0.032) and longer PFS (P = 0.015). Liver metastasis (P = 0.007) and combined systemic therapy (P = 0.036) were significantly associated with DCR, but not associated with PFS or OS. Conclusions: Some patients with advanced gastric cancer can benefit from apatinib. This study help us to identify patients who has potential benefit from apatinib.

Apatinib for patients (pts) with advanced soft tissue sarcoma (STS) after chemotherapy: A prospective, open-label, single-arm, multicentered study.

11553 Background: The development of STS therapeutics has been challenging, especially patients who failed chemotherapy. Anti-angiogenesis inhibitors had shown activity in STS, Apatinib is a TKI targeting on VEGFR-2 which has shown activity in many solid tumors. Methods: A Phase II, open-label, Single-arm, multicentered study was conducted in previously treated pts with advanced STS in China. The patients received apatinib 500mg orally qd in a 28-day-cycle, until disease progression or unacceptable adverse events. Antitumor response assessment was performed every 8 weeks per RECIST V1.1. The primary endpoint was PFS rate in 6 months and secondary endpoint was ORR and OS. Results: As cut-off on Jan 20th 2019, a total of 53 patients were enrolled in 9 centers, 51 patients received at least 2 cycles of Apatinib, 1 patient is still in treatment. The main histological subtypes were alveolar soft part sarcoma(n = 11), synovial sarcoma(n = 6), leiomyosarcoma (n = 6), clear cell sarcoma(n = 6) and undifferentiated pleomorphic sarcoma(n = 5). Overall, 27 of 51 patients were progression free at six months and the 6-m PFS rate was 53.32% (95%CI 37.76%, 66.63%). Until final follow-up, the ORR was 18.75% (9/48) and DCR was 87.5% (42/48). Additionally, median PFS was 7.13 (95%CI 3.84, 9.23) months and median OS has reached up to 24.67 (9.30-NE) months. Adverse events (AEs) were detected among all pts, hypertension and proteinuria are the most common AEs, occurred in 84.91% and 73.57% pts respectively. Grade 3/4 related adverse events were detected in 86.79% of pts, Grade 3/4 hypertension was the most common grade3/4 AE (56.60%). Conclusions: Overall, the present study demonstrates that apatinib has a clinically meaningful anti-tumor activity in pretreated STS pts, showing durable responses and prolonged overall survival. Some of the pts had a long-time benefit from the treatment. Apatinib was safe and generally well tolerated. Further studies on specific STS subtypes would be meaningful. Clinical trial information: NCT03064243 .

Effectiveness and Safety of Apatinib in Patients with Advanced or Metastatic Adenocarcinoma of Stomach or Gastroesophageal Junction: A Prospective Observation Study.

BackgroundApatinib showed promising efficacy in the treatment of advanced or metastatic gastric cancer (mGC) in previous clinical studies. However, the real-world data are limited, and this study aimed to assess the effectiveness and safety of apatinib for the treatment of advanced or mGC in this setting.MethodsIn this prospective observational study, progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and treatment-related adverse events (AEs) were recorded and evaluated. Univariate and multivariate analyses were conducted to explore potential biomarkers which might be related to the effectiveness.ResultsA total of 321 mGC patients from 47 centers in China were enrolled between July 1, 2015, and March 1, 2018. Thirty-two patients achieved partial response, 155 patients achieved stable disease, and 115 patients had progressive disease, and no CR was achieved, illustrating an ORR of 10.60% and a DCR of 61.92%. The median PFS and OS were 4.0 and 8.2 months, respectively. Multivariate Cox analysis showed that the potential biomarkers associated with longer PFS were combination regimens plus taxel/docetaxel, and apatinib initial dosage ≥500mg, occurrence of AEs of leukopenia, and hand-foot syndrome. Main AEs were proteinuria (17.1%), hypertension (15.9%), and handfoot syndrome (8.7%).ConclusionThe present prospective observational study showed favorable effectiveness and safety of apatinib in real-world patients with advanced or metastatic GC in China. (A prospective, multi-center, non-intervention study of apatinib in the treatment of advanced gastric cancer-Trial Registry Number: ChiCTR-OPN-15006601).

Apatinib for Treatment of Inoperable Metastatic or Locally Advanced Chondrosarcoma: What We Can Learn About the Biological Behavior of Chondrosarcoma from a Two-Center Study.

PurposeFor patients who have chondrosarcoma in the unresectable setting, antiangiogenic agents are reportedly effective. This multicenter, retrospective study investigated the antitumor activity of apatinib in patients with unresectable chondrosarcoma to gain insight into the biological behavior of this disease.MethodsAll of the patients with unresectable chondrosarcoma who were diagnosed between October 1, 2009, and November 1, 2019, in two sarcoma centers affiliated with Peking University were evaluated. Relevant information was collected from the medical records at both centers, from which patients receiving apatinib for systemic therapy were selected for analysis.ResultsIn total, efficacy analysis was conducted in 33 patients with a median follow-up time of 22.1 (Q1, Q3, 14.6, 23.0) months. There were 20/33 (60.0%) conventional chondrosarcomas (grades 2–3), 5/33 (15.2%) dedifferentiated chondrosarcomas, 4/33 (12.1%) mesenchymal chondrosarcomas, 3/33 (9.1%) extraskeletal myxoid chondrosarcoma, and 1/33 (3.1%) clear-cell chondrosarcomas with 87.9% in metastatic and 12.1% in locally advanced states. The objective response rate was 6/33 (18.2%). The median progression-free survival (PFS) was 12.4 months (Q1, Q3, 7.0, 21.2), while the median overall survival has not yet been reached. Rare variants of chondrosarcoma tended to have a longer PFS than conventional chondrosarcoma (P=0.06). Based on clinicopathological factors Cox and univariate analysis, only extraskeletal myxoid chondrosarcoma and baseline target lesions <60 mm benefited from the drug apatinib (P=0.14 and P=0.00), respectively. Grade 3 or higher adverse events were frequent in 11/33 (39.3%) of patients who discontinued apatinib due to deterioration of their general condition.ConclusionApatinib had clinically meaningful activity in patients with inoperable high-grade chondrosarcoma. However, special caution should be made in managing toxicity due to the indolent behavior and slow growth pattern after using this drug. Patients with a smaller tumor size and extraskeletal myxoid chondrosarcoma subtype might benefit from this therapy more.Clinical Trial RegistrationRegistered February 7, 2020, with clinicaltrials.gov: NCT04260113.

A Prospective Study of Apatinib in Patients with Extensive-Stage Small Cell Lung Cancer After Failure of Two or More Lines of Chemotherapy.

BackgroundBecause of rapid disease progression and lack of optimal treatment strategies beyond the second‐line, the prognosis of patients with extensive‐stage (ES) small cell lung cancer (SCLC) still remains depressing. Alternative treatment strategies are required to improve their prognosis. In this prospective clinical study, we aimed to evaluate the feasibility of single‐agent apatinib, a vascular endothelial growth factor receptor‐2 tyrosine kinase inhibitor, as a treatment option for patients with ES‐SCLC after failure of at least two prior chemotherapy regimens.Materials and MethodsTwenty‐two patients with ES‐SCLC treated with 500 mg single‐agent apatinib as subsequent‐line regimen in our institution from November 2016 to August 2018 were enrolled in the study. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs).ResultsClinical outcomes included partial response in 3 patients (13.6%), stable disease in 18 patients (81.8%), and disease progression in 1 patient (4.5%), with an ORR of 13.6% and DCR of 95.5%. The median PFS and OS were 5.4 and 10.0 months, respectively. Apatinib demonstrated a manageable toxicity profile, with grade I–III secondary hypertension and proteinuria as the most common AEs. No grade IV and V AEs were observed among the patients. Multivariate analysis revealed secondary hypertension as an independent predictor of OS (p = .047); however, the association became insignificant after Q correction (p = .455).ConclusionsApatinib was safe and effective in the management of patients with ES‐SCLC and can be considered as a treatment option after failure of at least two prior chemotherapy regimens. http://ClinicalTrials.gov identifier. NCT02995187Implications for PracticeThis study indicated the acceptable toxicity profile and promising efficacy of apatinib in the management of patients with extensive‐stage small cell lung cancer after failure from at least two prior chemotherapy regimens. Secondary hypertension can be a potential prognostic factor for apatinib treatment.

Efficacy and Safety of Apatinib in the Treatment of Postoperative Recurrence of Fibrosarcoma.

ObjectiveTo evaluate the efficacy and safety of apatinib in patients with relapse after surgery for fibrosarcoma.MethodsWe reviewed the clinical data of 56 patients who experienced recurrence after fibrosarcoma resection and who received chemotherapy from September 2015 to September 2017 (no significant difference in general data of patients) (p>0.05). Differences in drug use and adverse effects were observed between patients who received monotherapy and those who received regular chemotherapy (MAID/AI).ResultsCompared with the regular chemotherapy group, patients in the apatinib monotherapy group exhibited an improved overall response rate (ORR) and disease control rate (DCR). In patients treated with apatinib, the incidence of adverse reactions was improved, and the symptoms were mild (P<0.05).ConclusionApatinib is a single-drug regimen that can be used in cases of recurrence of fibrosarcoma with high expression of vascular endothelial growth factor receptor-2 (VEGFR-2); its short-term efficacy is excellent, and its side effects are minimal. This drug may be used as part of a regular chemotherapy program.

Adverse events and management of apatinib in patients with advanced or metastatic cancers: A review.

Apatinib (YN968D1) is a novel and highly selective tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor-2 (VEGFR-2) and is approved as a third-line and subsequent-line treatment for advanced gastric adenocarcinoma or gastroesophageal junction adenocarcinoma in China. Apatinib is also widely studied in other solid tumors. With the increase in clinical research of apatinib, its adverse effects have also received widespread attention. Hence, this article summarizes the pharmacological properties of apatinib and reviews its clinical use in advanced or metastatic cancers. We highlight the common adverse reactions of apatinib in clinical applications and we also clarify the corresponding prevention and intervention measures. Overall, this review will help us better understand the safety and efficacy of apatinib treatment.

Transarterial chemoembolization combined with microwave ablation and apatinib in patients with Barcelona clinic liver cancer Stage C hepatocellular carcinoma

Apatinib combined with transarterial chemoembolization (TACE) has shown promising results in cases of Barcelona clinic liver cancer Stage C (BCLC C) hepatocellular carcinoma (HCC). This study aimed to investigate the efficacy and safety of TACE in combination with microwave ablation (MWA) and apatinib. A retrospective, single.center study was undertaken using a one.to.one propensity score matching (PSM) analysis design and involved BCLC C HCC patients who underwent treatment with TACE.MWA.apatinib or TACE alone between January 2013 and June 2018. The patients were recommended to administer 500mg apatinib per day, combined with MWA and TACE. The adverse effects of apatinib, MWA. and TACE.related complications, progression.free survival (PFS), and overall survival (OS) were assessed. Of the 149 patients with BCLC C HCC who underwent TACE.MWA.apatinib or TACE alone, 131 were included in our study. Among them, 21 (16.0%) received TACE.MWA.apatinib and 110 (84.0%) underwent TACE alone. After PSM, twenty pairs were enrolled into different treatment groups. Patients in the TACE.MWA.apatinib group had a significantly longer median PFS than patients in the TACE.alone group on both before (median, 8.9 vs. 1.7 months, P = 0.0002) and after PSM (median, 5.4 vs. 2.1 months, P = 0.001). They also had a significantly longer median OS than patients in the TACE.alone group on before (median, 24.4 vs. 5.8 months, P = 0.000007) and after PSM (median, 24.4 vs. 5.4 months, P = 0.00005). The combination of apatinib, TACE, and MWA in BCLC C HCC patients is safe and effective. Toxicity is manageable by adjusting the apatinib dosage.

Efficacy and safety of apatinib as third- or further-line therapy for patients with advanced NSCLC: a retrospective study.

Background:Apatinib, an oral small-molecule angiogenesis inhibitor, selectively inhibits vascular endothelial growth factor receptor 2 (VEGFR-2), which inhibits vascular endothelial growth factor (VEGF) stimulated endothelial cell migration and proliferation and decreases tumour growth and metastasis. Recently, the efficacy of multi-target angiogenic drugs has been demonstrated for many cancers, including non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to evaluate the clinical efficacy of apatinib in patients with advanced NSCLC.Patients and methods:We conducted a retrospective analysis of 70 patients with advanced NSCLC who received second-line and later treatment from November 2015 to July 2017 with poor results. Out of the 70 patients, 36 patients received apatinib treatment after second-line or later treatment, whereas 34 patients in the control group did not receive further treatment. The patients were treated with oral apatinib 500 mg once a day every day for 4 weeks per cycle. Treatment was continued in responding and stable patients until disease progression or intolerable toxicity. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and side effects of the drug were recorded and reviewed.Results:ORR, DCR, PFS, and OS were evaluated in 36 patients receiving apatinib and 34 patients in the control group. The ORR and DCR in patients receiving apatinib therapy were 22.2% and 77.8%, respectively. The median PFS and OS in the treatment group were 5.6 and 9.6 months, respectively. The median OS in the apatinib group was significantly longer than that in the control group (9.6 versus 3.8 months; p < 0.0001). In contrast, there were no differences in adverse reactions between the patients in the treatment and control groups.Conclusion:Apatinib showed favourable efficacy and safety and can thus be used as a treatment option for patients with advanced NSCLC.

526P - A phase II study of apatinib in patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC)

BackgroundNo standard treatment strategy for patients with recurrent/metastatic esophageal squamous cell carcinoma (ESCC) experiencing progression after one or more lines of chemotherapy. The aim of this study was to assess the efficacy and safety of apatinib, an oral vascular endothelial growth factor receptor 2 (VEGFR-2) tyrosine kinase inhibitor, in patients with recurrent/metastatic ESCC for whom at least one line of prior chemotherapy had failed. MethodsThis was a phase II trial that enrolled patients with recurrent/metastatic ESCC who had evidence of disease progression after first-line or more lines chemotherapy. All patients received continuous apatinib 500mg once daily until disease progression, death, or intolerable toxicity, dose escalation was allowed. The primary end point was progression free survival (PFS). ResultsBetween July 2017 and August 2018, 40 patients were recruited. Data was cutoff at June 26, 2019. Among the 40 patients, 5 patients achieved partial response while 21 had stable disease. Primary end point median PFS (mPFS) was 113 days (95% 45-180). Median OS (mOS) was 158 days (95% 101-215), Objective response rate (ORR) was 12.5%. The incidence of drug-related adverse events (AEs) was 87.5%. 40.0% patients developed severe AEs. Main AEs were Fatigue (37.5%), Hand-foot syndrome (27.5%) and Hypertension (25%). Two patients with massive hemoptysis, and two patients with tracheal esophageal fistula had the uncontrolled primary tumor or trachea/bronchi eroded. ConclusionsThe study confirmed that apatinib was effective as second-line or more lines treatment for recurrent/metastatic ESCC patients, and most adverse effect were acceptable. However, patients with uncontrolled primary tumor or trachea/bronchi eroded should been cautiously considered to use. Clinical trial identificationNCT03274011. Legal entity responsible for the studyFudan University Shanghai Cancer Center. FundingJiangsu Hengrui Medicine. DisclosureAll authors have declared no conflicts of interest.

Clinical Value Of Apatinib As A Salvage Treatment In Patients With Chemo-Refractory Advanced Cervical Cancer.

PurposeApatinib is effective and safe for several advanced or metastatic cancers, but its therapeutic value in cervical cancer is still unknown. The aim of the study was to assess the therapeutic value of apatinib in patients with chemo-refractory advanced cervical cancer.Patients and methodsThis was a retrospective study of patients with advanced cervical cancer treated with apatinib between April 2015 and December 2018 at the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China. Patients had to have failed at least 2 lines of chemotherapy prior to receiving apatinib. The clinical tumor response was evaluated after 4 weeks of apatinib treatment, and then every 8 weeks (two cycles). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events were evaluated.ResultsTwenty-five patients were included in this study. The median PFS was 5.8 months (95% CI, 4.65–6.95), and the median OS was 12.2 months (95% CI, 8.99–15.41). ORR was 48% and DCR was 96%. Complete response was not observed. The most common adverse events in this study (all grades) were hand-foot syndrome (48%), hypertension (20%), and mouth mucositis (20%).ConclusionApatinib monotherapy showed good therapeutic value with tolerable adverse events for patients with chemo-refractory advanced cervical cancer.

Application effect of apatinib in patients with failure of standard treatment for advanced malignant tumours

BackgroundIn recent years, targeted therapy has received widespread attention. Among these therapies, anti-angiogenic targeted drugs have become one of the hotspots of research. Apatinib is a novel oral small molecule anti-angiogenic agent that has been clinically tested in a variety of solid tumours. The aim of this study was to investigate the efficacy of apatinib in patients with advanced malignant tumours and failure of standard therapy.MethodsWe collected 41 patients with advanced malignant tumours in our department; all tumours were pathologically confirmed as malignant. All patients received apatinib after failure of standard therapy: 500 mg/dose, one dose/d, orally 30 min after a meal, until progressive disease or intolerable adverse reactions occurred. When there was a second- or third-degree adverse reaction associated with apatinib during treatment, apatinib treatment could be suspended or reduced to 250 mg/dose. Clinical efficacy and progression-free survival were assessed according to RECIST1.1, and adverse reactions were observed.ResultsEfficacy assessment was available for 31 patients with a median progression-free survival time of 2.66 months; the objective response rate and disease control rates were 16.1 and 64.5%, respectively. The disease control rates of the patients with lower Eastern Cooperative Oncology Group scores (1–2 points) and with fewer metastatic sites (< 3 sites) were higher than those of the patients with higher scores (3 points) and with more metastatic sites (≥3 sites), respectively (all P < 0.05). The most common adverse reactions were hypertension, neutropenia and hand-foot syndrome.ConclusionFor patients with advanced malignant tumours with failure of standard therapy, administration of apatinib can still result in good efficacy. The efficacy of apatinib is better in patients with a higher performance status and lower degree of tumour progression.

803P - Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer

BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to systematically evaluate the efficacy and safety of apatinib targeted therapy in advanced AFPGC and investigate the predictive factors of apatinib treatment. MethodsThree hundred thirty-seven patients were enrolled in the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer. Among them, we recruited all the patients identified with AFPGC for this study. The clinical features, efficacy, adverse events, and survival were assessed. ResultsWe enrolled 21 patients with AFPGC into this study. The objective response rate (ORR) of apatinib in patients with AFPGC was 10%, whereas the disease control rate (DCR) was 70%. The median progression-free survival (PFS) was 3.5 months [95%confidence interval (CI): 2.34-4.66]. The median overall survival (OS) was 4.5 months (95%CI: 3.49-5.51). The common grade adverse events (AEs) were hypertension (33.3%), fatigue (23.8%), and myelosuppression (19.0%). The most common grade 3 to 4 AEs were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%). Carcinoembryonic antigen (CEA) elevation was considered to be a potential independent predictive factor (P=0.030). ConclusionsApatinib 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. Clinical trial identificationAHEAD-G202 (NCT02668380). Editorial acknowledgementElsevier Language Editing Services. Legal entity responsible for the studyThe author. FundingJiangsu HengRui Medcine Co., Ltd.; 2016 PUMCH Science Fund for Junior Faculty (Pumch-2016-1.13); Chinese Anti-cancer Association (CORP-143-09). DisclosureThe author has declared no conflicts of interest.

Apatinib in patients with extensive-stage small-cell lung cancer after second-line or third-line chemotherapy: a phase II, single-arm, multicentre, prospective study

BackgroundSmall-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies.MethodsEligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate.ResultsForty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand–foot syndrome, increased L-gamma-glutamyltransferase.ConclusionsApatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted.Trial registrationNCT02945852.

The Efficacy And Safety Of Apatinib Treatment For Patients With Metastatic Or Recurrent Cervical Cancer: A Retrospective Study.

BackgroundThis study was performed to assess the efficacy and safety of apatinib in patients with metastatic or recurrent cervical cancer.MethodsTwenty-six patients with metastatic or recurrent cervical cancer and treated with apatinib until progressive disease or unacceptable toxicity were included in this multicenter, retrospective, observational study from January 2016 to April 2018. The primary end point was progression free survival (PFS). Secondary end points included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and toxicity. Toxicities were assessed according to Common Terminology Criteria for Adverse Events.ResultsA total of 26 metastatic or recurrent cervical cancer patients were enrolled in this study. No complete response (CR) occurred, 4 patients (15.4%) showed partial response (PR), 11 patients (42.3%) had stable disease (SD), and 11 patients (42.3%) had progressive disease (PD), with DCR of 57.7% and ORR of 15.4%. Median progression-free survival (PFS) was 3.0 months (95% confidence interval [CI]: 0–6.3 months) and overall survival (OS) was 7.0 months (95% CI: 5.1–8.9 months) respectively. The most common adverse effects were hand-foot syndrome (50.0%), secondary hypertension (26.9%) and fatigue (26.9%). Three patients discontinued treatment due to grade 3 toxicities (one case for hand-foot syndrome, two cases for diarrhea) and 6 patients required dose reduction because of adverse effects.ConclusionApatinib seems active in heavily-pretreated metastatic or recurrent cervical cancer. The adverse effects were moderate but manageable.

Quantification of the Plasma Concentration of Apatinib by 2-Dimensional Liquid Chromatography.

Apatinib is a new oral micromolecular tyrosine kinase inhibitor, which is mainly used as a third-line treatment for chemotherapy-refractory advanced metastatic gastric cancer patients. However, apatinib has shown dose titration and severe adverse reactions in clinical practice. Quantification of plasma concentrations of apatinib may be an effective method to balance the clinical efficacy and adverse reactions. The purpose of this study was to develop and validate a 2-dimensional liquid chromatography method for the measurement of apatinib in plasma. The analysis of apatinib was performed using a 2-dimensional high-performance liquid chromatography system. We precipitated the proteins with acetonitrile. The mobile phases consisted of a first-dimensional mobile phase (acetonitrile:methanol:25 mmol·L ammonium phosphate = 25:25:50, V/V/V, pH adjusted to 7.2 using phosphoric acid) and a second-dimensional mobile phase (acetonitrile:10 mmol·L ammonium phosphate = 28:72, vol/vol, pH adjusted to 3.7 using phosphoric acid). The ultraviolet detection wavelength was set at 340 nm. The temperature of the detector cell was 40°C, and the injection volume was 500 μL. The range of calibration curve was 15.27-1491.48 ng/mL. The accuracy and imprecision were within ±2.23% and less than 10.22%, respectively (intraday and interday). The range of recovery was 97.45%-108.92%. The intraday and interday relative SDs (reproducibility) of high-performance liquid chromatography retention times were less than 0.18% and 0.46%, respectively. In the clinical assessment, the dose range of apatinib mesylate for patients with gastric cancer was 250-500 mg every day (2-60 days), resulting in trough plasma concentrations between 272.7 and 727.8 ng/mL. A simple, convenient, accurate, and robust 2-dimensional liquid chromatography method was developed and verified, which successfully determined the plasma concentrations of apatinib in patients with gastric cancer.