Safety Of Apatinib In Treatment Research Articles

Abstract 5249: Efficacy and safety of apatinib in treatment of unresectablehepatocellular carcinoma: A real-world study

Abstract Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Apatinib is a small molecule TKI inhibitor. Its efficacy and safety for unresectable HCC patients have been demonstrated in randomized controlled clinical studies. However, the efficacy and safety of apatinib in real world is lacking. We are aiming to evaluate the efficacy and safety of apatinib in real world.MethodsPatients of older than 18 years with unresectable HCC confirmed by IHC (Immunohistochemistry) or CT and MR Imaging were enrolled in the study. All patients received apatinib monotherapy or combined with other treatments including TACE and chemotherapy. The enrolled patients were treated until disease progression, death, or severe intolerable toxicity, etc. The primary endpoint was overall response rate (ORR), and secondary endpoints were disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). The adverse events (AEs) were also recorded.ResultsFrom February, 2019 to May, 2020, a total of 233 patients were enrolled. Among them, 66 (28.33%) patients received apatinib monotherapy and 167 (71.67%) patients received combination therapy. Patients with a history of hepatitis accounted for 70%. 8 patients achieved complete response (CR), 64 patients achieved partial response (PR), 120 patients achieved stable disease (SD), and 41 patients had progressive disease (PD), illustrating an ORR of 30.90% and a DCR of 82.40%. Median PFS and OS were 6.93 months (95% CI, 6.19-7.68 months) and 11.36 months (95% CI, 9.96-12.77 months), respectively. The safety profile indicated that the most common drug-related adverse events were hypertension (37.90%), hand-foot-skin reaction (27.39%), fatigue (19.11%), thrombocytopenia (16.02%). Grade 3/4 treatment related AEs included thrombocytopenia (4.30%), hypertension (3.82%), neutropenia (2.73%). After symptomatic treatment, all the adverse events were treated properly, and no unexpected adverse events were observed. Conclusions In current study, apatininb showed good tolerance with acceptable toxicity and high tumor response rate that translated into promising PFS and OS in unresectable HCC patients. ChiCTR1900021822 Citation Format: Jun Liu, Guangbing Li, Qiang He, Shijun Sun, Chuanlin Zhao, Chuandong Sun, Bo Zhang, Yi Cui, Yongqiang Ye, Xuting Zhi, Shiping Li, Shiping Li, Guozheng Pan, Changlin Ma, Jinhua Hu, Jun Li, Suling Wang, Yuangang Qiao, Wanhua Ren, Qi Meng. Efficacy and safety of apatinib in treatment of unresectablehepatocellular carcinoma: A real-world study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5249.

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 in Treatment of Unresectable Intrahepatic Cholangiocarcinoma: An Observational Study.

PurposeUnresectable intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib for patients with unresectable ICC.Patients and MethodsA total of 10 patients with unresectable ICC were enrolled for this single-center observational study between March 2, 2016, and August 27, 2019. Subjects received 500 mg apatinib on a daily basis. Tumor response was assessed by 1.1 response evaluation criteria in solid tumors. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method. The drug-related adverse effects were also monitored.ResultsBased on the follow-up computed tomography and magnetic resonance imaging after treatment, 4 (40.0%), 4 (40.0%), and 2 (20.0%) patients achieved a partial response, stable disease, and progression of the disease, respectively. The response rate and disease control rate were 40.0% and 80.0%, respectively. The median PFS was 4.5 months (95% confidence interval: 3.157~5.843 months); the median OS was 6.5 months (95% confidence interval: 4.744~8.256 months). Furthermore, 3-, 6-, and 9-month OS rates were 77.5%, 61.7%, and 15.0%, respectively. The most common hematologic grade 3 adverse event was neutropenia (10%); the most common nonhematologic grade 3 adverse events were hypertension (20.0%) and hand-foot syndromes (20.0%). No treatment-related grade 4 or 5 adverse events were recorded.ConclusionApatinib revealed to have antitumour activity in unresectable ICC patients, with manageable toxicities, and thus might be used as a new treatment option for patients with unresectable ICC.

Efficacy and safety of apatinib in treatment of osteosarcoma after failed standard multimodal therapy: An observational study.

Recently, apatinib has been shown to be effective in treating sarcoma. This study aimed to assess the safety and efficacy of apatinib in the treatment of patients with osteosarcoma after failed of standard multimodal therapy and to compare the therapeutic effects of apatinib on osteosarcoma between high-dose group and low-dose group.A total of 27 patients with osteosarcoma who received apatinib between January 2016 and August 2017 were retrospectively reviewed. Among the 27 patients, the objective response rate (ORR) and the disease control rate (DCR) were 25.93% and 66.67%, respectively. The median of progression-free survival (m-PFS) was 3.5 months (95% confidence interval [CI], 2.5–4.8 months), and the median of overall survival (m-OS) was 9.5 months (95% CI, 7.8–10.5 months). There was no statistically significant difference in ORR (36.36% vs 18.75%), DCR (63.64% vs 68.75%), m-PFS (4.3 months [95% CI, 1.8–7 months) vs 3.35 months (95% CI, 1.8–4 months]), and m-OS (9.5 months [95% CI, 7.8–10.5 months] vs 9.4 months [95% CI, 7.8–10.8 months]) (P > .05) between the high-dose group (the average dose was 659 mg/qd) and the low-dose group (the average dose was 516 mg/qd). Most of the adverse events (AEs) were in grade 1 or grade 2. The main AEs in grade 3 were hypertension, rash, weight loss, hand-foot syndrome, and diarrhea.Apatinib is safe and effective in the treatment of advanced osteosarcoma. We recommend that the initial dose of apatinib should be 500 mg/qd in the treatment of osteosarcoma.

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.

Clinical efficacy and safety of apatinib in treatment of alpha fetoprotein-positive advanced gastric cancer.

e15513 Background: Alpha fetoprotein (AFP)-producing gastric cancer (APGC) is a minor subtype of gastric cancer (GC) with high malignancy, rapid progress, high metastatic rate and poor prognosis. Treatment of AFP-positive GC is not different from that of AFP-negative GC, but the efficacy can not match for the latter. Apatinib, a novel inhibitor of VEGFR-2, has achieved survival improvement in advanced GC patients. We aimed to evaluate the efficacy and safety of apatinib in AFP-positive advanced gastric cancer patients. Methods: This was a single-arm, open-label, exploratory study design. Eligibility criteria included histologically proven GC; patient age 18-75 years; AFP-positive; clinical stage III or IV; and ECOG performance status of 1 or 2. A history of receiving previous treatment was not required. All the patients were orally given apatinib at an initial dose of 500 mg (qd) until disease progression or death. Dose reduction to 250 mg was allowed. Results: A total of 16 pts including 15 males and 1 female were eligible. The median age was 62.5 years (range 26-74 years). Poorly differentiated adenocarcinoma was the main histological type, and the main metastatic sites were liver (12/16) and abdominal (2/16). Ten pts received gastric surgery and 13 had previous chemotherapy prior to apatinib, and 10 patients received chemotherapy along with apatinib. Among the 16 pts, 14 were available for the efficacy evaluation. Two pts achieved partial response (PR), 10 had stable disease (SD), and 2 had progressive disease (PD). The objective response rate (ORR) and the disease control rate (DCR) were 14.3% (2/14) and 85.7% (12/14), respectively. All pts were included for safety analysis. The incidence of adverse events (AEs) was 87.5%. Main AEs were bone marrow suppression (43.75%), hypertension (50%), and abdominal pain (31.25%). Conclusions: Administration of apatinib make clinical benefit to AFP positive advanced gastric cancer with a comparable disease control and tolerable adverse reactions. Clinical trial information: ChiCTR-OPC-16008295. Clinical trial information: ChiCTR-OPC-16008295.