Treatment Of Apatinib Research Articles

Efficacy and safety of apatinib combined with nab-paclitaxel for second-line treatment of metastatic triple negative breast cancer (TNBC): An open-label phase II trial.

e13127 Background: Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Preclinical studies have demonstrated that apatinib can enhance the anti-tumor effect of taxanes in TNBC via promoting apoptosis and suppressing migration and invasion of tumor cells. Previous studies have also shown the role of apatinib in combination with chemotherapy for treating TNBC. However, combinational treatment of apatinib and nab-paclitaxel for metastatic TNBC has not been reported. Therefore, the objective of this study was to evaluate the safety and efficacy of apatinib in combination with nab-paclitaxel as a second-line treatment for TNBC. Methods: This is a single-center, single-arm, and open-label prospective study. The patients enrolled in this study had metastatic TNBC, ECOG PS 0-2, at least one measurable lesion, and had previously received one systemic therapy except apatinib and nab-paclitaxel. They were treated with apatinib (250mg, PO, QD) plus nab-paclitaxel (125mg/m2, IV, day 1, 8 and 15) every 3 weeks as second-line treatment until disease progression, unacceptable toxicity, or consent withdrawal. The study utilized RECIST v1.1 to assess efficacy and NCI-CTCAE 5.0 to report adverse events. The study's primary endpoints were tolerability and progressive free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR). Results: Twenty patients were enrolled by the cut-off date of December 1st, 2023. The median age was 55 years (range 31-76) and all had an ECOG PS of 0-1. Ninety percent of the sample had a Ki67 of 30% or higher, while 85% tested negative for PD-L1. All patients had distant metastases, with 35.0% having visceral metastasis and 35% having metastatic sites of 3 or more. 70% of patients had undergone surgery on the primary tumor. All patients received apatinib plus nab-paclitaxel treatment, with a median of 9 cycles (range 2-25), were included in the safety dataset. All patients experienced grade 1-2 treatment-related adverse events (TRAEs). Haematological toxicity of grade 3-4 with neutropenia occurred in 25.0% of patients. In addition, non-haematological toxicities were observed in 10% of patients, including abnormal hepatic function (5.0%) and hypertension (5.0%). No treatment-emergent adverse event (TEAE) resulted in death during the study. Out of the 20 evaluated patients, the median progression-free survival (PFS) was 6.7 months (95% CI: 6.0-NR). The objective response rate (ORR) was 65.0% (13/20), and the disease control rate (DCR) was 90.0% (18/20), according to RECIST v1.1. The median overall survival (OS) has not yet been reached. Conclusions: The combination of apatinib and nab-paclitaxel showed promising antitumor activity in patients with metastatic TNBC as a second-line treatment, with a manageable safety profile. Clinical trial information: NCT05019690 .

The FGF6 amplification mutation plays an important role in the progression and treatment of malignant meningioma

Meningioma is a benign tumor with slow growth and long course. However, patients with recurrent malignant meningioma still face a lack of effective treatment. Here, we report a rare case of primary mediastinal malignant meningioma with lung and bone metastases, who benefited from the treatment of apatinib (≥33 months) and anlotinib (until the publication date). Retrospective molecular analysis revealed the frequent amplification of FGF6 in primary and metastatic lesions. Then we constructed the FGF6 over-expressed IOMM-LEE and CH157MN malignant meningioma cell lines, and in vitro and vivo experiments showed that overexpression of FGF6 can promote the proliferation, migration and invasion of malignant meningioma cells. Based on the Western analysis, we revealed that FGF6 can promote the phosphorylation of FGFR, AKT, and ERK1/2, which can be inhibited by anlotinib. Together, we were the first to verify that overexpression of FGF6 promotes the progression of malignant meningiomas by activating FGFR/AKT/ERK1/2 pathway and pointed out that anlotinib may effectively inhibit the disease progression of patients with FGF6 amplification.

Apatinib potentiates the therapeutic effect of anti-PD-1 in locally advanced head and neck cancers.

Antiangiogenic inhibitors have been shown to synergize with immune checkpoint blockade, but the underlying mechanisms of the synergistic response are not fully understood. We investigate the impact of VEGFR2 inhibition on tumor-infiltrating immune cells invivo and the activity of the combination of apatinib and anti-PD-1 in synergistic mouse model of HNSCC. A patient with squamous cell carcinoma of the left tongue with cervical lymph node were received with combined induction treatment of camrelizumab and apatinib to validate the efficacy of neoadjuvant immunotherapy before surgery. We found that apatinib increased the infiltration of CD8+T cells and decreased the population of Tregs in a preclinical syngeneic mouse model. The proportions of CD8+PD1+T cells were significantly increased in apatinib-treated tumors. The combined treatment of apatinib and anti-PD-1 demonstrated better therapeutic benefit than each treatment alone. The patient with squamous cell carcinoma of the left tongue with cervical lymph node achieved major pathologic response (MPR) after two cycles of combined induction treatment. Our study demonstrated that apatinib therapy synergized with an anti-PD-1 antibody in preclinical cancer models and in patient with advanced HNSCC. These results provide a new rationale for advancing this neoadjuvant immunotherapy in large scale of clinical trials of HNSCC.

Efficacy of apatinib combined with temozolomide in the treatment of recurrent high‑grade glioma: A meta‑analysis.

Recurrent high-grade glioma is a refractory disease, and its prognosis is poor. Although the treatment of apatinib combined with temozolomide provides improved efficacy and is able to prolong survival, this conclusion has been based on small samples. In order to clarify this treatment's efficacy, a meta-analysis was performed in the present study. Different databases were screened and finally, 10 studies were included, comprising 357 patients with recurrent high-grade gliomas. The efficacy and prognosis were analyzed using Stata software. The results indicated that the overall objective response rate (ORR) and disease control rate (DCR) of apatinib combined with temozolomide were 0.36 (95% CI, 0.26-0.46) and 0.86 (95% CI, 0.82-0.89), respectively. Subgroup analysis indicated that the overall ORR was 0.43 (95% CI, 0.29-0.57) and 0.26 (95% CI, 0.14-0.38), and the DCR was 0.89 (95% CI, 0.85-0.93) and 0.76 (95% CI, 0.69-0.84) in the treatment of apatinib with temozolomide dose-dense group and the conventional-dose group (5/28 regimen), respectively. Further prognostic analysis indicated that the median overall survival of patients with high-grade glioma treated with apatinib combined with temozolomide was 8.21 months (95% CI, 7.20-9.22 months) and the median progression-free survival was 5.45 months (95% CI, 4.53-6.37). Analysis of the publication bias of the effect size revealed that there was bias in the DCR, while no bias was found in the remaining effect size (ORR, median overall survival and median progression-free survival). After correction by the trim-and-fill method, bias was indicated to have no significant impact on the results. In conclusion, apatinib combined with temozolomide has the effect that, compared with traditional Bevacizumab treatment, it can improve the efficacy in the treatment of recurrent high-grade glioma and improve prognosis. When combining with dose-dense temozolomide, the effect may be better than that of the conventional 5/28 regimen.

The clinical efficacy and safety of TACE combined with apatinib for advanced hepatocellular carcinoma: A propensity score matching analysis.

The combined treatment of transcatheter arterial chemoembolization (TACE) and apatinib had beneficial effects on the survival of patients with advanced hepatocellular carcinoma (HCC), but the efficacy of this regimen is still controversial and needs further investigation. The clinical records of advanced HCC patients between May 2015 and December 2016 were collected from our hospital. They were categorized into the TACE monotherapy group and the combination of TACE and apatinib group. After propensity score matching (PSM) analysis, the disease control rate (DCR), objective response rate (ORR), progression-free survival (PFS), and occurrence of adverse events were compared between the two treatments. There were 115 HCC patients included in the study. Among them, 53 received TACE monotherapy and 62 were treated with TACE plus apatinib. After PSM analysis, 50 pairs of patients were compared. The DCR of the TACE group was significantly lower than that of the combination of TACE and apatinib group (35 [70%] versus 45 [90%], P < 0.05). The ORR of the TACE group was also significantly lower than that of the combination of TACE and apatinib group (22 [44%] versus 34 [68%], P < 0.05). Patients who received the combined treatment of TACE and apatinib had longer PFS compared with those in the TACE monotherapy group ( P < 0.001). Moreover, hypertension, hand-foot syndrome, and albuminuria were more common in the combination of TACE and apatinib group ( P < 0.05), although all adverse events were well tolerated. The combined treatment of TACE and apatinib showed beneficial effects on tumor response, survival outcomes, and tolerance to treatment, which may be used as a routine regimen for advanced HCC patients.

SYST-04 PRELIMINARY REPORT OF A CLINICAL TRIAL EVALUATING THE SAFETY AND EFFICIENCY OF NEOADJUVANT CAMRELIZUMAB AND APATINIB IN PATIENTS WITH RECURRENT HIGH-GRADE GLIOMAS: A PROSPECTIVE, PHASE II, SINGLE-ARM STUDY

High-grade glioma is the most common malignant primary brain tumor in the central nervous system. Multiple strategies such as surgery, radiotherapy, and chemotherapy have been used, but the prognosis of patients with high-grade glioma remains poor. No standard treatment exists for recurrent gliomas; however, combination therapies of programmed cell death protein 1 blockades with antiangiogenic agents have demonstrated promising effects in different solid tumors. We have initiated a clinical trial designed to evaluate the safety and efficiency of neoadjuvant therapy using camrelizumab and apatinib in patients with recurrent highgrade gliomas. In this prospective, Phase II, singlearm study, patients with recurrent highgrade gliomas will receive singledose intravenous injection of camrelizumab (200 mg) and daily oral administration of apatinib (250 mg/day for 7 days) 14 days before surgery for recurrent tumor. Sequential therapy will begin 2 weeks after surgery with the biweekly injection of camrelizumab and 4 weeks after surgery with the daily administration of apatinib. Treatment of camrelizumab and apatinib will be continued until disease progression or unacceptable toxicity or death. The trial is planned to enroll 30 patients. Up-to date (March 31, 2022), 12 patients had been enrolled, in which, 9 were GBM. Three patients died, while 4 cases on trial more than 6 months, the longest already 1 year. Although an evaluation is still impossible to be conducted yet, some patients have shown a promising outcome. We will present updated results on the meeting. These preliminary data suggest that this study would be worthwhile. This study was approved by the Ethics Committee of Sun Yatsen University Cancer Center (Guangzhou, China; approval No. SLB202014901). This study was registered with ClinicalTrials.gov under identifier NCT04588987.

Hepatic artery infusion chemotherapy (HAIC) combined with apatinib and camrelizumab for hepatocellular carcinoma (HCC) in BCLC stage c: A prospective, single-arm, phase II trial (TRIPLET study).

4106 Background: The combination of anti-angiogenesis and immune checkpoint blockade has been proven to improve clinical outcomes of advanced HCC. We assessed the efficacy and safety of HAIC combined with apatinib and camrelizumab for BCLC stage C HCC. Methods: Consecutive treatment-naive patients with BCLC stage C HCC were enrolled in this phase II trial (NCT04191889). Eligible patients were administrated with HAIC (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2 and fluorouracil 2500 mg/m2; q3w), combined with apatinib (250 mg qd) and camrelizumab (200 mg q3w) for 6 cycles, followed by maintenance therapy with apatinib and camrelizumab until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR). Following an optimal Simon 2-stage design, 26 eligible patients needed to be included in the first stage, of whom at least 11 patients had to achieve objective responses to warrant further investigation in the second stage. Results: In the first stage, confirmed ORR was achieved in 16 and 20 patients per RECIST v1.1 and mRECIST, respectively, therefore enrollment of the second stage continued. From 4/13/2020 to 1/31/2022, 31 eligible patients were enrolled and 29 evaluable for efficacy analyses. The 31 patients were characterized with median age 45 years (range 30-67), men 96.77%, Child-Pugh A 100%, portal vein tumor thrombus Vp 1-2/Vp 3-4 25.81%/45.16%, and extrahepatic metastasis 12.90%. As of 1/31/2022, with a median follow-up of 18.07 months (95% CI 14.10 to 22.04), the confirmed ORR was 70.96% (95% CI, 53.41%-83.91%) with 22 partial responses (PR) per RECIST v1.1,while 87.10% (95% CI, 71.15%-94.87%) with 3 (9.68%) complete responses (CR) and 24 (77.42%) PR per mRECIST. The disease control rate (DCR) was 87.10% (95% CI, 71.15%-94.87%) whether per RECIST v1.1 or mRECIST. The median time to response (TTR) was 2.67 months (interquartile range (IQR), 1.43-2.96) per RECIST v1.1 and 2.03 months (IQR, 1.37-2.80) per mRECIST. The median progression-free survival (PFS) time was 9.37 months (95% CI 7.00 to 11.73) per RECIST v1.1 and 9.63 months (95% CI 5.82 to 13.44) per mRECIST, in particular, the liver-specific median PFS time was 10.80 months (95% CI 5.88 to 15.72) per mRECIST. The 6-month, 12-month, and 18-month overall survival rate were 93.1%, 85.8%, and 65.8%, respectively. Grade ≥3 adverse events (AEs) occurred in 74.19% of the patients, of which the most common AEs were decreased neutrophils (52.17%), decreased lymphocytes (43.38%), and increased ALT and AST (30.43% and 43.48% for each). Conclusions: The triplet treatment of HAIC, apatinib and camrelizumab showed promising clinical benefits and acceptable safety for BCLC Stage C HCC. Further confirmatory randomized controlled trial is about to get underway. Clinical trial information: NCT04191889.

PD-1 inhibitors combined with apatinib for advanced diffuse gastric cancer: A retrospective study.

e16009 Background: Numerous studies have shown that immunotherapy has a synergistic effect when combined with targeted drug therapy. Apatinib has been proven effective in advanced gastric cancer. Based on these facts and to assess the efficacy and safety of programmed death 1 (PD-1) inhibitors and apatinib as combination therapy in patients (pts) with unresectable locally advanced or metastatic diffuse gastric cancer(DGC), a retrospective clinical research study was carried out. Methods: Retrospective analysis of a cohort of pts with advanced diffuse gastric cancer received treatment of apatinib combined with PD-1 inhibitors enrolled in our institution between January 2019 and January 2021.Pts (n = 34) received PD-1 inhibitors and apatinib (250mg once daily) in this retrospective study. Overall survival (OS) and progression free survival (PFS) were estimated by Kaplan Meier curves, and other endpoints included objective response rate(ORR), disease control rate(DCR), prognostic factors. Results: A total of 34 pts were enrolled in a real-world dataset from Henan Cancer Hospital. 2 pts achieved partial response(PR),17 pts had stable disease(SD),and 15 pts had progressive disease (PD). The ORR and DCR were 5.88% (2/34) and 55.88% (19/34), respectively. The median PFS(mPFS) was 2.47 months (95%CI:1.9-3.0), and the median OS (mOS) was 6.80 months (95%CI 3.7-9.9). Pts with less than 3 metastatic sites had longer mOS than those with more metastatic sites(2.70 vs. 7.73 P &lt; 0.05). And in this study, the levels of platelet, albumin, CEA, CA199, CA125 and LDH affect patients’ prognosis. Kaplan-Meier analyses revealed that patients with normal platelet had better mOS than those with higher platelet(mOS 7.10 vs 0.3; P &lt; 0.05).And similar results were found in the pts with normal albumin. The mOS of those was longer than the pts with lower or higher albumin(7.73 vs 2.20 vs 2.53, P &lt; 005). And we demonstrated that positive groups of CEA(&gt; 4.7ng/ml), CA125(&gt; 35U/ml), CA199(&gt; 27U/ml) and LDH(&gt; 245U/L) were significantly associated with worse outcomes than that of negative groups(all P &lt; 0.05). The incidence of grade 3 or 4 treatment-related adverse events (TRAEs) was 26.5%(9/34). These adverse events (AEs) included pruritus, rash, hand-foot syndrome, hypertension and increased aspartate aminotransferase (AST) or alanine aminotransferase (ALT). No treatment-related deaths occurred. Conclusions: Combination therapy of PD-1 inhibitors and apatinib showed encouraging clinical activity and demonstrated tolerable toxicity in pts with advanced DGC. The level of platelet, albumin, CEA, CA199, CA125 and LDH could predict the prognosis of DGC patients.

The Fibrillin-1/VEGFR2/STAT2 signaling axis promotes chemoresistance via modulating glycolysis and angiogenesis in ovarian cancer organoids and cells.

BackgroundChemotherapy resistance is a primary reason of ovarian cancer therapy failure; hence it is important to investigate the underlying mechanisms of chemotherapy resistance and develop novel potential therapeutic targets.MethodsRNA sequencing of cisplatin‐resistant and ‐sensitive (chemoresistant and chemosensitive, respectively) ovarian cancer organoids was performed, followed by detection of the expression level of fibrillin‐1 (FBN1) in organoids and clinical specimens of ovarian cancer. Subsequently, glucose metabolism, angiogenesis, and chemosensitivity were analyzed in structural glycoprotein FBN1‐knockout cisplatin‐resistant ovarian cancer organoids and cell lines. To gain insights into the specific functions and mechanisms of action of FBN1 in ovarian cancer, immunoprecipitation, silver nitrate staining, mass spectrometry, immunofluorescence, Western blotting, and Fӧrster resonance energy transfer‐fluorescence lifetime imaging analyses were performed, followed by in vivo assays using vertebrate model systems of nude mice and zebrafish.ResultsFBN1 expression was significantly enhanced in cisplatin‐resistant ovarian cancer organoids and tissues, indicating that FBN1 might be a key factor in chemoresistance of ovarian cancer. We also discovered that FBN1 sustained the energy stress and induced angiogenesis in vitro and in vivo, which promoted the cisplatin‐resistance of ovarian cancer. Knockout of FBN1 combined with treatment of the antiangiogenic drug apatinib improved the cisplatin‐sensitivity of ovarian cancer cells. Mechanistically, FBN1 mediated the phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2) at the Tyr1054 residue, which activated its downstream focal adhesion kinase (FAK)/protein kinase B (PKB or AKT) pathway, induced the phosphorylation of signal transducer and activator of transcription 2 (STAT2) at the tyrosine residue 690 (Tyr690), promoted the nuclear translocation of STAT2, and ultimately altered the expression of genes associated with STAT2‐mediated angiogenesis and glycolysis.ConclusionsThe FBN1/VEGFR2/STAT2 signaling axis may induce chemoresistance of ovarian cancer cells by participating in the process of glycolysis and angiogenesis. The present study suggested a novel FBN1‐targeted therapy and/or combination of FBN1 inhibition and antiangiogenic drug for treating ovarian cancer.

Abstract P2-14-08: Preliminary safety and efficacy results of camrelizumab in combination with apatinib and eribulin in heavily pretreated patients with advanced triple-negative breast cancer: A phase II trial

Abstract Background: Our prior phase II trial (NCT03394287) demonstrated that camrelizumab (an anti-PD-1 antibody) combined with apatinib (an anti-VEGFR2 tyrosine kinase inhibitor) showed a favorable objective response rate (ORR) of 43% in treating patients with advanced triple-negative breast cancer (TNBC), even in those with PD-L1-negative tumors and received 1-2 lines of chemotherapy. However, the progression-free survival (PFS) and overall survival (OS) remained short. Since EMBRACE trial and 301 study found that eribulin monotherapy significantly prolonged OS with relatively low toxicities than other common chemotherapy drugs as multi-line therapy in the treatment of advanced breast cancer, especially for patients with TNBC, we have conducted a phase II trial to study the efficacy and safety of combinational treatment of camrelizumab, apatinib, and eribulin in patients with heavily pretreated advanced TNBC. Methods: Female patients with advanced TNBC who were previously treated with at least one line of systemic therapy were enrolled from three academic hospitals in China to receive camrelizumab 200mg (iv. 3mg/kg for the patient whose weight is below 50kg) on day 1, and apatinib 250mg daily (po, d1-d21), plus eribulin mesylate at 1.4 mg/m2 (iv.) on days 1 and 8 of a 21-day cycle until progression, unacceptable toxicities or patient withdrawal. The primary endpoint was ORR according to RECIST v1.1. Secondary endpoints included disease control rate (DCR), clinical benefit rate (CBR), PFS, time to response (TTR), duration of response (DoR), 12-months OS, toxicities, and potential biomarkers. Results: From March 2020 to May 2021, 46 patients were enrolled. 13 of 46 patients (28.3%) received ≥3 lines of chemotherapy in the advanced setting. And 8 of 46 patients (17.4%) had received PD-1/PD-L1 blockade combined with chemotherapy in the previous treatment for advanced disease. Until May 31th, 2021, 39 and 46 patients were evaluable for overall response and safety, respectively. The ORR was 40.0% (16 of 40, 95% CI: 24.9-56.7), and 3 patients achieved complete response (CR) (intention-to-treat analysis). The DCR was 90.0% (95% CI: 76.3-97.2) (intention-to-treat analysis). The median TTR was 1.5 (95% CI: 1.4-3.0) months. The median PFS was 8.2 (95% CI: 4.9 - not reached) months. 23 patients (50.0%) were still on treatment. Neither PD-L1 status (CPS score) nor lines of prior systemic therapies was correlated with ORR (P=0.782 and 0.651, respectively). All patients suffered from treatment-related adverse events (TRAEs) of any grade, while 34.8% of patients had experienced grade 3 or 4 TRAEs. Key grade 3 or 4 TRAEs were thrombocytopenia (13.0%), leukopenia (13.0%), and elevated aspartate aminotransferase (8.7%). No treatment-related deaths were observed. Conclusions: Camrelizumab in combination with apatinib and eribulin showed favorable efficacy and measurable toxicities in treating heavily pretreated patients with advanced TNBC. This trial is currently ongoing. ClinicalTrials.gov number, NCT04303741. Summary of clinical response in the intention-to-treat population.ParameterOverall (n=40)ORR, %16 (40.0; 24.9-56.7)DCR, %36 (90.0; 76.3-97.2)Median TTR, m1.5 (1.4-3.0)Median PFS, m8.2 (4.9-not reached)The data are presented in the form of n (%; 95% CI), or median time (95% CI). Citation Format: Jieqiong Liu, Zhenluan Tian, Ying Wang, Ying Lin, Hengyu Li. Preliminary safety and efficacy results of camrelizumab in combination with apatinib and eribulin in heavily pretreated patients with advanced triple-negative breast cancer: A phase II trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-08.

Initial report of a clinical trial evaluating the safety and efficiency of neoadjuvant camrelizumab and apatinib in patients with recurrent high-grade gliomas: A prospective, phase II, single-arm study

Background and Aim: High-grade glioma is the most common malignant primary brain tumor in the central nervous system. Multiple strategies such as surgery, radiotherapy, and chemotherapy have been used, but the prognosis of patients with high-grade glioma remains poor. No standard treatment exists for recurrent gliomas; however, combination therapies of programmed cell death protein 1 blockades with antiangiogenic agents have demonstrated promising effects in different solid tumors. Therefore, since the end of 2020, a clinical trial designed to evaluate the safety and efficiency of neoadjuvant therapy using camrelizumab and apatinib in patients with recurrent high-grade gliomas has been carried out in our institution. Methods/Design: In this prospective, Phase II, single-arm study, patients with recurrent high-grade gliomas will receive single-dose intravenous injection of camrelizumab (200 mg) and daily oral administration of apatinib (250 mg/day for 7 days) 14 days before reoperation for tumor resection. Sequential therapy will begin 2 weeks after surgery with the biweekly injection of camrelizumab and 4 weeks after surgery with the daily administration of apatinib. Treatment of camrelizumab and apatinib will be continued until disease progression or unacceptable toxicity or death. The primary outcome measure will be the median overall survival rate. Secondary outcome measures will include progression-free survival rate at 6 months and at 12 months and other measures. The trial is planned to enroll 30 patients. This study was approved by the Ethics Committee of Sun Yat-sen University Cancer Center (Guangzhou, China; approval No. SL-B2020-149-01) on July 27, 2020. Results and Conclusions: Although an evaluation is still impossible to be conducted yet, 11 patients had been enrolled by the end of January 2022. Some patients have shown a promising outcome. These preliminary data suggest that this study would be worthwhile. We hope that this study will provide scientific evidence to better care of patients with recurrent high-grade glioma. Trial registration: This study was registered with ClinicalTrials.gov under identifier NCT04588987 on October 19, 2020.

A Comparison of Chemotherapy Used with and without Apatinib for Patients with Ovarian Carcinoma Who Progressed after Standard Regimens: A Systematic Review and Meta-Analysis.

Objective This meta-analysis was conducted to compare the therapeutic efficacy and clinical safety of the combination therapy of apatinib plus chemotherapy with that of chemotherapy alone in patients with refractory or recurrent ovarian carcinoma (OC). Methods Relevant randomized controlled trials (RCT) or case-control studies (CCS) were identified by searching Chinese and English databases up to October 31, 2020. The risk of methodological bias tool and Newcastle–Ottawa scale (NOS) were used to assess trial quality. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the therapeutic effects and adverse drug reactions. Subgroup analyses of study type, study sample size, dosage of apatinib, and chemotherapy regimen between treatment group and control group were performed. Publication bias was assessed by funnel plot symmetry, Begg–Mazumdar test, and Egger test. The robustness of our results was presented by removing the trial one by one. Results Fifteen eligible studies covering 1,020 patients were included in this review and meta-analysis. Among these studies, 8 were RCTs, and 7 were CCSs. Compared with chemotherapy alone, apatinib plus chemotherapy significantly increased objective response rate (OR = 3.55; 95% CI 2.31 to 5.47), disease control rate (OR = 3.04; 95% CI 2.12 to 4.36), and overall survival (OR = 5.03; 95% CI 3.16 to 6.90). Conclusions The combination treatment of apatinib plus chemotherapy provides better clinical benefits for OC patients when compared to chemotherapy alone and should be recommended for suitable patients with OC after the failure of standard regimens. However, further investigation into future large-scale prospective randomized research is still needed.

Effective treatment of apatinib for chemotherapy-refractory advanced gastric carcinoma with AFP-secretion and HER2-positivity: A case report.

α-fetoprotein (AFP)-secreting gastric cancer (AFP-GC) is a relatively rare, aggressive malignancy among all GC types. However, no GC case with simultaneous expression of AFP and epidermal growth factor receptor 2 (HER2) has been reported to date. To the best of our knowledge, the present report was the first to describe the use of apatinib to treat a patient with advanced GC characterized by AFP-secretion and HER2-positivity. An 86-year-old man with advanced GC was diagnosed with AFP-secretive and HER2-positive GC with liver metastasis at The Affiliated Hospital of Jiujiang University (Jiujiang, China). The patient received first-line (i.e., S-1 plus oxaliplatin) and second-line (i.e., docetaxel) chemotherapy combined with trastuzumab for two cycles, respectively. However, the disease progressed rapidly. Subsequently, apatinib was administered as third-line therapy. After two cycles of apatinib therapy, the patient reported the disappearance of upper abdominal pain and an improvement in his appetite. Furthermore, the AFP level had sharply decreased to 620 ng/ml. Subsequently, upper abdominal computed tomography imaging revealed that the gastric lesion and liver metastatic lesion had reduced in size by 67% and 24%, respectively, suggesting partial remission. Currently, the patient has continued to receive apatinib therapy. It was speculated that AFP-secretion status could contribute to the chemoresistance of HER2-positive GC. Apatinib may be a promising anticancer agent in the case of advanced AFP-producing and HER2-positive GC.

Clinical efficacy and safety of apatinib as maintenance treatment in patients with advanced esophageal squamous cell carcinoma

ABSTRACT Background: To investigate the clinical efficacy, safety and prognostic factors of apatinib therapy as maintenance treatment in patients with advanced esophageal squamous cell carcinoma. Methods: We selected 46 patients with advanced esophageal squamous cell carcinoma treated with radiotherapy and chemotherapy in our hospital from January 2017 to February 2019, all of whom were treated with apatinib. We analyzed the clinical efficacy, adverse reactions and prognostic factors. Meanwhile, the expression of VEGFR-2 and NF-kB was detected by the immunohistochemical SABC method. Results: The oral treatment of apatinib in the VEGFR-2 and NF-kB positive groups was better than that in the negative groups. The disease control rate was 67.39%. The main adverse reactions were hypertension (60.87%). The degree of adverse reactions was mainly grade 1-2. Cox multivariate regression analysis showed that the degree of adverse reactions and ECOG score were independent factors affecting OS in patients with advanced esophageal squamous cell carcinoma. Conclusion: The positive expression of VEGFR-2 and NF-kB is expected to be the molecular target of oral apatinib targeted therapy for esophageal cancer. Apatinib has a certain clinical effect as the maintenance treatment for advanced esophageal squamous cell carcinoma patients, with mild adverse reactions and high safety.

Efficacy and safety of apatinib combined with transarterial chemoembolization (TACE) in treating patients with recurrent hepatocellular carcinoma.

BackgroundApatinib, a vascular endothelial growth factor receptor 2 (VEGFR-2) inhibitor, has shown promising therapeutic effect for hepatocellular carcinoma (HCC). This prospective clinical study was implemented to evaluate the efficacy and safety of apatinib combined with transarterial chemoembolization (TACE) versus TACE alone in treating patients with recurrent HCC after hepatectomy.MethodsEligible patients with postoperative recurrent HCC from January 2018 to January 2020 were enrolled at the Xinqiao Hospital of Army Medical University. Patients were randomized 1:1 into TACE plus apatinib group or TACE-alone group. The clinical information of patients was collected, and the patients were followed up until untreatable progression or the end of the study. Adverse events (AEs), overall survival (OS) and progression-free survival (PFS) between the two groups were evaluated. In addition, the objective response rate (ORR) and the disease control rate (DCR) were determined according to the modified Response Evaluation Criteria In Solid Tumors (mRECIST). Among those indexes, PFS was the primary endpoint.ResultsThis study enrolled 80 patients with recurrent HCC, and the demographics and primary tumor characteristics were balanced between the two groups. However, TACE plus apatinib treatment could significantly improve the median PFS of patients when compared with the TACE-alone group (17.2 vs. 12.5 months, P=0.041). The 1- and 2-year overall survival (OS) rates showed a tendency of improving in the TACE plus apatinib group, but not significantly (95.0% vs. 85.0%, and 90.0% vs. 75.0%; both P>0.05). Furthermore, the TACE plus apatinib treatment did significantly increase the short-term ORR and DCR when compared with the TACE-alone group (all P<0.05). And no unexpected toxicity or procedure-related mortality was occurred during this study.ConclusionsThe combination treatment of apatinib and TACE might be safe and of potential benefit on patients with intrahepatic recurrent HCC.

Effectiveness and safety of low-dose apatinib in advanced gastric cancer: A real-world study.

Apatinib has been demonstrated to be effective and safe among patients with gastric cancer failing after at least two lines chemotherapy. This study aimed to evaluate its effectiveness and safety of low‐dose apatinib for the treatment of gastric cancer in real‐world practice. We performed a prospective, multicenter observation study in a real‐world setting. Patients with advanced gastric cancer more than 18 years old were eligible and received low‐dose apatinib (500 mg or 250mg per day) therapy. The median progression‐free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were assessed. Between September 2017 and April 2019, a total of 747 patients were enrolled. The mPFS was 5.56 months (95% CI 4.47‐6.28), and mOS was 7.5 months (95% CI 6.74‐8.88). Four patients achieved complete response, 47 achieved partial response, and 374 patients achieved stable disease. The ORR was 6.83% and DCR was 56.89%. In addition, multivariate Cox regression analysis indicated that hand‐foot syndrome was one independent predictor for PFS and OS. The most common adverse events (AEs) at any grade were hypertension (36.55%), proteinuria (10.26%), hand‐foot syndrome (33.53%), fatigue (24.9%), anemia (57.35%), leukopenia (44.49%), thrombocytopenia (34.21%), and neutropenia (53.33%). Grade 3‐4 AEs with incidences of 5% or greater were anemia (13.97%), thrombocytopenia (7.14%), and neutropenia (6.67%). No treatment‐related death was observed during the treatment of apatinib. The prospective study suggested that low‐dose apatinib was an effective regimen for the treatment of advanced gastric cancer with tolerable or controlled toxicity in real world.Trial registration: NCT03333967.

A comparison of transcatheter arterial chemoembolization used with and without apatinib for intermediate- to advanced-stage hepatocellular carcinoma: a systematic review and meta-analysis.

BackgroundHepatocellular carcinoma (HCC) is a common cancer worldwide and prognosis for patients with the disease remains poor. Most patients are diagnosed at an advanced stage and are only eligible for palliative therapy. As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), apatinib has a certain antitumor effect for a variety of solid tumors. In clinical practice, clinicians have attempted to treat intermediate- to advanced-stage HCC patients with a combination of transcatheter arterial chemoembolization (TACE) and apatinib. However, a consensus on the therapeutic effects of this treatment is yet to be reached. This meta-analysis was conducted to compare the therapeutic efficacy and clinical safety of the combination therapy of TACE plus apatinib with that of TACE alone in patients with intermediate- to advanced-stage HCC.MethodsRelevant studies were identified by searching PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), Chinese Science and Technology Periodical Database (VIP) and the reference lists of retrieved articles up to July 31, 2019. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to express the therapeutic effects of TACE plus apatinib versus TACE on survival, objective response rate, disease control rate, progressive disease rate and adverse events using a mixed-effect model. Subgroup analyses of study type, dosage of apatinib, TACE regimen, study sample size between treatment groups and control groups were performed. Publication bias was assessed using fail-safe N, Begg-Mazumdar test and Egger’s test.ResultsFrom 23 eligible studies, a total of 1,342 patients were included in this review and meta-analysis. Among these studies, 18 were randomized clinical trials and 5 were case-control studies. Compared with those being treated with TACE alone, patients receiving TACE plus apatinib showed significantly better half-year survival (OR, 2.741, 95% CI, 1.745–4.306) and 1-year survival (OR, 2.284, 95% CI, 1.442–3.620). The superiority of TACE and apatinib over TACE monotherapy was evident in the disease control rate (OR, 2.919, 95% CI, 2.184–3.903), objective response rate (OR, 2.683, 95% CI, 2.099–3.429) and progressive disease rate (OR, 0.341, 95% CI, 0.255–0.456), respectively.ConclusionsThe combination treatment of apatinib and TACE provides better survival benefits for intermediate- to advanced-stage HCC patients when compared to TACE monotherapy and should be recommended for suitable patients with unresectable HCC. However, further investigation into future prospective clinical studies is warranted.

Efficacy and Safety of Apatinib Combined with Etoposide in Patients with Recurrent Platinum-resistant Epithelial Ovarian Cancer: A Retrospective Study.

Purpose: Advanced epithelial ovarian cancer (EOC) eventually develops into a recurrent platinum-resistant disease. The response to standard treatment and prognosis in patients with EOC is generally unsatisfactory. This study aimed to assess the efficacy and safety of apatinib combined with etoposide in patients with recurrent platinum-resistant EOC.Materials and Methods: This is a single-center, retrospective, observational study. We have reviewed a total of 33 patients with recurrent platinum-resistant EOC from July 2017 to July 2018, who were regularly treated with apatinib and etoposide until disease progression or unacceptable toxic effects occurred.Results: At the date of the review finished, 15 of 33 (45.5%) patients remained on the combined treatment of apatinib and etoposide, while the other 18 (54.5%) had discontinued. Although no complete response (CR) occurred, the overall response rate (ORR) and disease control rate (DCR) were 36.4% and 78.8% respectively. The median progression-free survival (PFS) was 5.6 months (95% CI, 4.1~7.1), and the median overall survival (OS) was 10.3 months (95% CI, 9.4~11.2). The most common adverse event was mucositis oral (60.6%), which caused the treatment discontinued in 4 (12.1%) patients. Other relatively common adverse events were hand-foot syndrome (42.4%), hypertension (39.4%), nausea or vomiting (30.3%), neutropenia (24.2%), fatigue (24.2%) and thrombocytopenia (21.2%). Grade 1 and 2 adverse events accounted for 63.6% (21/33).Conclusion: The efficacy of apatinib combined with etoposide is encouraging in patients with platinum-resistant EOC. Most adverse events of this combined therapy were mild and tolerable. Severe mucositis oral was not rare, which needs more precautions.

Efficacy and safety observation of apatinib in treatment of advanced gastric cancer

Objective To investigate the effect and safety of apatinib in the treatment of advanced gastric cancer. Methods A total of 60 patients with advanced gastric cancer at the first Affiliated Hospital of Hainan Medical College from April 2015 to October 2018 were retrospectively analyzed, and all patients were divided into two groups according to the treatment method, each group of 30 cases. The control group was treated with conventional treatment, and the observation group was given the treatment of apatinib on the basis of the control group, and then the clinical curative effect and adverse reactions were compared between the two groups. Results There were 2 cases (6.67%) of complete remission in the observation group, 14 cases (46.67%) of partial remission, 10 cases (33.33%) of stability and 4 cases (13.33%) of disease progression, and the total effective rate was 53.33% (16/30). The control group had no complete remission, 8 cases (26.67%) of partial remission, 11 cases (36.67%) of stability and 11 cases (36.67%) of disease progression, and the total effective rate was 26.67% (8/30). The difference of total effective rate between the two groups was statistically significant (χ 2 = 4.444, P = 0.035). There was no significant difference in the level of tumor marker carcinoembryonic antigen (CEA), carbohydrate antigen (CA)199, CA125, cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) between the two groups before and after treatment (all P > 0.05). The incidence of hand-foot syndrome and hypertension in the observation group was higher than that in the control group [73.33% (22/30) vs. 43.33% (13/30), H = 5.554, P = 0.018; 76.67% (23/30) vs. 46.67% (14/30), H = 5.711, P = 0.017]. The incidence of proteinuria, bone marrow suppression and the cardiac adverse reactions in the observation group was higher than that in the control group [63.33% (19/30) vs. 33.33% (10/30), H = 3.300, P = 0.069; 60.00%(18/30) vs. 36.67% (11/30), H = 5.455, P = 0.071; 53.33% (16/30) vs. 30.00% (9/30), H = 3.360, P = 0.067]. Conclusion Apatinib is effective in the treatment of advanced gastric cancer, but the occurrence of hand-foot syndrome and hypertension should be paid close attention during the treatment. Key words: Stomach neoplasms; Tumor markers, biological; Molecular targeted therapy; Apatinib; Comparative effectiveness research; Adverse effects

Therapeutic effect of small molecule targeting drug apatinib on gastric cancer and its role in prognosis and anti-infection mechanism.

ObjectiveTo investigate the effect of apatinib when treating advanced gastric cancer (GC) as well as the mechanism of preventing infection. Methods: From January 2017 to December 2018, 100 advanced GC patients had failed to receive second-line or above treatment in XX Hospital were divided into two groups according to the experimental requirements: the experimental group and the blank group. The experimental group was treated with small molecule targeted drug apatinib, while the blank group was only treated with ordinary drugs. After 4 weeks of treatment, the diagnosis and evaluation were carried out every eight weeks. In this study, the mechanism of infection prevention and prognosis was studied through the internal treatment of GC patients with apatinib. Results: until the end of the fourth week, a significant difference can be seen in the treatment effect between the experimental group as well as the blank group. In the experimental group, the proportion of partial remission + disease stability reached about 73%, while that in the blank group was only about 33%. In addition, apatinib was better than the blank group in the control of adverse reactions like hypertension, proteinuria, myelosuppression as well as diarrhea. In addition, apatinib was better than the blank group when treating AFP positive GC. In terms of the therapeutic effect of apatinib, it is much better than that of the negative group. In addition, apatinib is also better than the blank group in drug resistance for GC patients. It is found that apatinib’s anti infection mechanism is to prevent the phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2) as well as stop the downstream signal pathway, so as to inhibit the tumor angiogenesis, tumor growth and metastasis, so as to achieve treatment and reduce the probability of infection. Conclusion: the therapeutic effect of small molecule targeting drug apatinib on gastric cancer is better than that of other drugs, whether in therapeutic effect, drug resistance, adverse reactions or infection control. This study has important reference significance for the follow-up treatment of apatinib and cancer.