Efficacy Of Apatinib Research Articles

Drug-related adverse events potentially predict the efficacy of apatinib on advanced hepatocellular carcinoma

BackgroundHepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related deaths worldwide every year, and most HCC patients are diagnosed with advanced disease and can only receive systemic treatment. TKIs are the most important components of the systemic treatment of HCC and have both good efficacy and adverse events (AEs). MethodsThis analysis included 207 patients with locally advanced unresectable or metastatic HCC who received oral treatment with apatinib. We analyzed the overall survival (OS) and progression-free survival (PFS) of patients with or without corresponding AEs to evaluate which AEs can predict the efficacy of apatinib.ResultsPatients with hand-foot syndrome (HFS; p = 0.005), proteinuria (p = 0.006) and diarrhea (p < 0.001) had significantly better OS than those without corresponding AEs, and the appearance of HFS (p = 0.006) and proteinuria (p = 0.004) was associated with longer PFS.ConclusionAmong all the AEs induced by apatinib in the treatment of advanced HCC, proteinuria could potentially predict PFS, and diarrhea was a potential predictor of OS.

Anti-proliferation effects of Apatinib in combination with Curcumin in breast cancer cells.

Despite remarkable development of new therapeutic strategies to improve survival rates and treatment of patients with cancer, there are still many limitations in management of patients with distant metastasis breast cancer. Therefore, the aim of this study was to investigate a novel method to enhance therapeutic efficacy of Apatinib (as a chemotherapeutic agent) by co-administration of Curcumin (as a bioactive herbal compound) in breast cancer treatment. Effects of Apatinib, Curcumin, and their combinations (Apa-Cur) was evaluated on viability and proliferation of breast cell line (MCF7) by MTT assay. Moreover, effects of Apatinib, Curcumin, and Apa-Cur was investigated on apoptosis rate in the cancer cells. Expression levels of apoptosis-related genes (BAX, SMAC, BCL2, and SURVIVIN) in treated cancer cells and untreated controls were evaluated using the Real-Time PCR method. The obtained results showed that all treatments of Apatinib, Curcumin, and Apa-Cur significantly decreased viability and proliferation of the breast cancer cells in a concentration- and time-dependent manner. However, anti-proliferation activity of Apa-Cur combination was significantly higher than Apatinib and Curcumin treatment alone. In addition, Apatinib, Curcumin, and Apa-Cur increased apoptosis percentage in the treated cancer cells through regulation of apoptosis-related genes expression. In general, Apa-Cur combination therapy exerts more profound anti-proliferation effects on breast cancer cell than Apatinib or Curcumin monotherapy. However, further studies are required to identify other possible signaling pathways and mechanisms involved in the anticancer effects of Apatinib, Curcumin, and Apa-Cur.

Efficacy and safety of apatinib in advanced refractory soft tissue sarcoma and association with histologic subtypes: a multicenter retrospective study.

BackgroundAntiangiogenic therapy is a potential strategy against advanced refractory soft tissue sarcoma (STS). This retrospective study aimed to assess the efficacy and safety of apatinib in patients with advanced refractory STS and explore its clinical effect on the different histologic subtypes.MethodsPatients with pathologically diagnosed and metastatic STS who had failed at least standard chemotherapy and were naive to angiogenesis inhibitors were enrolled in this multicenter respective study. Apatinib was administered orally at a dosage of 250 to 850 mg/day. The primary endpoints were objective response rate (ORR) and disease control rate (DCR). The secondary endpoints were progression free survival (PFS) and overall survival (OS). Tumor assessment was done after the first 4 weeks and every 8 weeks thereafter.ResultsTwenty-six patients were enrolled from seven centers between December 2015 and December 2020, consisting of 9 leiomyosarcomas (LMS), 4 rhabdomyosarcomas (RMS), 3 undifferentiated pleomorphic cell sarcomas (UPS), 3 fibrosarcomas (FS), 3 alveolar soft part sarcomas (ASPS), 2 angiosarcomas (AS) and 2 synovial sarcomas (SS). The median age was 49.0 [26–77] years, 15 females and 11 males. The ORR was 34.62% [9/26, 95% confidence interval (CI): 19.42–53.78%] and DCR was as high as 84.62% (22/26, 95% CI: 66.47–93.85%). The median progression-free survival and overall survival were 6.0 months (95% CI: 2.42–9.58) and 19.3 months (95% CI: 7.31–31.29) respectively. Furthermore, 181 patients from seven studies as well as this trial were included for pooled analysis of apatinib efficacy dependency on histology. In terms of ORR, RMS (41.7%), ASPS (78.6%), and Ewing sarcoma (40.7%) seemed to benefit more than the other histologic subtypes. Common adverse events (AEs) included hand-foot skin reaction (n=13, 50.0%), hypertension (n=12, 46.15%), proteinuria (n=10, 38.46%). Seven patients (7/26, 26.92%) had grade 3 AEs and no grade 4 AEs occurred. 2 patients (2/26, 7.69%) and 15 patients (15/26, 57.69%) experienced dose withdrawal and dose reduction respectively.ConclusionsApatinib showed promising efficacy and a manageable safety profile in patients with advanced refractory STS. In addition, the response to apatinib in STS seemed to be dependent on histology.

Phase 1 trial of apatinib combined with intensity-modulated radiotherapy in unresectable hepatocellular carcinoma

BackgroundTo investigate the maximum tolerated dose (MTD) of apatinib delivered during and after intensity-modulated radiotherapy (IMRT) for unresectable hepatocellular carcinoma (HCC).MethodsPatients with unresectable HCC who were not eligible for radiofrequency ablation (RFA), transcatheter arterial chemoembolization (TACE), or residual/ recurrent after the prior local treatment were enrolled. Patients were scheduled to be treated with IMRT at 50–60 Gy/25–30 fractions. Oral apatinib tablets were administered concurrently with IMRT and continued thereafter. We used a 3 + 3 dose-escalation design, with three dose levels of apatinib (250, 500, and 750 mg). Grade 3 or more severe adverse events (AEs) were defined as dose-limiting toxicities (DLTs). The treatment response was calculated using the Modified Response Evaluation Criteria in Solid Tumours.ResultsNine patients with Barcelona Clinic Liver Cancer Stage C were included. One patient withdrew from the apatinib 250 mg group and another patient was added. No DLTs occurred in the apatinib 250 mg group. Five patients were included in the apatinib 500 mg group, and 2 cases of DLT (grade 3 leukopenia) were found among them. Dose escalation was terminated and the MTD was determined to be 250 mg. Common grade 1–2 AEs included fatigue, hypertension, dizziness, bone marrow suppression, and hyperbilirubinemia. The median follow-up time for all patients was 16.0 months. Three patients achieved complete response and another three achieved partial response. The objective response rate was 6/9 (66.7%), and the disease control rate was 9/9 (100%). Three patients relapsed out of the radiation field. The median progression-free survival was 17.0 months, and the median overall survival was 16.7 months.ConclusionsWhen combined with IMRT, apatinib 250 mg daily was recommended for a phase 2 study of unresectable HCC. The antitumor activity of the combination treatment was encouraging. The safety and efficacy of apatinib combined with IMRT for unresectable HCC should be further investigated in future studies.Trial registrationRegistration No. ChiCTR1800018309. Registered 11 September 2018. Retrospectively registered, https://www.chictr.org.cn/showproj.aspx?proj=30461.

Activated amino acid response pathway generates apatinib resistance by reprograming glutamine metabolism in non-small-cell lung cancer

The efficacy of apatinib has been confirmed in the treatment of solid tumors, including non-small-cell lung cancer (NSCLC). However, the direct functional mechanisms of tumor lethality mediated by apatinib and the precise mechanisms of drug resistance are largely unknown. In this study, we demonstrated that apatinib could reprogram glutamine metabolism in human NSCLC via a mechanism involved in amino acid metabolic imbalances. Apatinib repressed the expression of GLS1, the initial and rate-limiting enzyme of glutamine catabolism. However, the broken metabolic balance led to the activation of the amino acid response (AAR) pathway, known as the GCN2/eIF2α/ATF4 pathway. Moreover, activation of ATF4 was responsible for the induction of SLC1A5 and ASNS, which promoted the consumption and metabolization of glutamine. Interestingly, the combination of apatinib and ATF4 silencing abolished glutamine metabolism in NSCLC cells. Moreover, knockdown of ATF4 enhanced the antitumor effect of apatinib both in vitro and in vivo. In summary, this study showed that apatinib could reprogram glutamine metabolism through the activation of the AAR pathway in human NSCLC cells and indicated that targeting ATF4 is a potential therapeutic strategy for relieving apatinib resistance.

MO18-2 A phase II trial of neoadjuvant apatinib combined with nab-paclitaxel and carboplatin in triple-negative breast cancer

Pathological complete response (pCR) is essential for improvements of prognosis in triple-negative breast cancer (TNBC). We evaluated the efficacy of apatinib combined with nab-paclitaxel and carboplatin in patients in this phase II clinical trial.

The efficacy and safety of apatinib in patients with recurrent or metastatic nasopharyngeal carcinoma: a systematic review and meta-analysis.

BackgroundApatinib is a small-molecule tyrosine kinase inhibitor targeting VEGFR-2, which was recently used in a phase II clinical trial for the treatment of recurrent or metastatic nasopharyngeal carcinoma (rmNPC). However, there is no consistent conclusion on its efficacy and safety on rmNPC. This study conducted a meta-analysis of clinical research on the efficacy and safety of apatinib in the treatment of rmNPC.MethodsIn April 2022, the PubMed, Web of Science, Scopus, Chinese National Knowledge Infrastructure (CNKI), CMB, and Wanfang databases were systematically searched, and relevant research literature were screened and analyzed. The clinical trial literatures using apatinib as the main single or combined treatment for rmNPC patients were selected and combined with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and other efficacy and safety indicators.ResultsThe meta-analysis included 12 studies, including 408 patients with rmNPC. The methodological index for nonrandomized studies scale was used to evaluate the bias of the included literatures and found that the bias was low. A total of 408 rmNPC patients were included in the included literature, with 11 studies being a phase II single-arm trial and one being a phase II non-randomized controlled trial. The ORR of patients with rmNPC treated with apatinib was 41.5% (95% CI: 34.8%, 48.2%), and the DCR was 80.2% (95% CI: 70.9%, 89.6%). The median PFS was 6.4 months (95% CI: 5.3, 7.4), and the median OS was 14.8 months (95% CI: 10.7, 18.9). The incidence of hypertension, hand-foot skin reaction, and proteinuria was 31% (95% CI: 19–43%), 29% (95% CI: 20–39%), and 13% (95% CI: 6–20%), respectively.DiscussionThe efficacy of apatinib in the treatment of rmNPC patients is similar to that of the previous second-line chemotherapy drugs, but since most studies are phase II single-arm studies, the advantages and disadvantages of the existing second-line chemotherapy regimens cannot be determined.

Efficacy and safety of apatinib as second or later-line therapy in extensive-stage small cell lung cancer: a prospective, exploratory, single-arm, multi-center clinical trial.

BackgroundA paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC.MethodsIn this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964.ResultsFrom 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3–8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5–24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6–7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed.ConclusionsApatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.

Efficacy of Apatinib plus S-1 Therapy in the Treatment of Advanced Gastric Cancer Patients and the Effect on the Levels of Tumor Markers and Th1 and Th2-Like Cytokines.

Objective To assess the efficacy of apatinib plus S-1 therapy in the treatment of advanced gastric cancer patients and the effect on the levels of tumor markers and Th1 and Th2-like cytokines. Methods From October 2019 to December 2020, 100 patients with advanced gastric cancer assessed for eligibility were recruited and assigned at a ratio of 1 : 1 to receive either S-1 regimen (tegafur, gimeracil, and oteracil potassium capsules) (observation group) or apatinib plus S-1 therapy (experimental group). Outcome measures included clinical efficacy serum tumor marker levels, Th1 and Th2-like cytokine levels, time to progression (TTP), overall survival (OS), and adverse events. Results The S-1 therapy plus apatinib was associated with a significantly higher efficacy versus S-1 therapy alone (P < 0.05). The eligible patients given S-1 therapy plus apatinib showed significantly lower levels of serum carcinoembryonic antigen (CEA), glycoantigen 199 (CA199), and glycoantigen 125 (CA125) versus those receiving S-1 therapy (P < 0.05). S-1 therapy plus apatinib outperformed the single therapy of S-1 therapy in mitigating the levels of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and interleukin-10 (IL-10) (P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P > 0.05). S-1 therapy plus apatinib was associated with a significantly shorter TTP (5.2 ± 0.7 months) and a longer OS (9.3 ± 2.5 months) versus S-1 therapy alone (7.1 ± 1.3, 5.1 ± 1.3 months) (P < 0.05). Conclusion The efficacy of apatinib plus S-1 therapy showed better improvement in lowering the serum tumor marker levels and ameliorating the Th1 and Th2-like cytokine levels versus S-1 therapy alone, so it is worthy of clinical application.

A Comparative Analysis of Efficacy of Apatinib Combined with Transarterial Chemoembolization and Transarterial Chemoembolization Alone in the Treatment of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

Background The treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) remains controversial due to the limited effect of sorafenib. The aim of the study was to investigate whether apatinib could improve the efficacy of transarterial chemoembolization (TACE) for patients with HCC complicated by PVTT. Methods The study included 109 patients with HCC and PVTT who received TACE combined with apatinib (TACE + apatinib) (53 patients) or TACE alone (56 patients) between June 2015 and January 2019. Propensity score matching (PSM) analysis was used to reduce the potential selection bias. Overall survival time (OS) and time to progression (TTP) were used to evaluate the efficacy of TACE + apatinib and TACE alone. Results Before PSM, TACE + apatinib significantly improved median TTP (7.0 vs. 3.0 months, P < 0.001) and median OS (15.0 vs. 7.0 months, P < 0.001) when compared with TACE alone. After PSM, the median TTP was significantly longer in the TACE + apatinib group, 6.0 months, than in the TACE alone group, 3.0 months (P < 0.001), and the median OS was significantly longer in the TACE + apatinib group, 14.0 months, than in the TACE alone group, 7.0 months (P < 0.001). Subgroup analysis revealed that, except for patients with Child–Pugh class B, the patients with or without extrahepatic metastases and with Child–Pugh class A had longer TTP and OS after the combined TACE + apatinib treatment than after TACE alone. Conclusion The combination of TACE + apatinib might be an effective and safe treatment for HCC patients with PVTT.

Efficacy and safety of apatinib combined with whole-brain radiation therapy with a simultaneous integrated boost for brain metastases from non-small cell lung cancer: a multicenter retrospective study.

BackgroundBrain metastases (BMs) develop in 20–65% of non-small cell lung cancer (NSCLC) patients and are associated with a poor prognosis. Apatinib, a tyrosine kinase inhibitor (TKI) that selectively inhibits the vascular endothelial growth factor receptor 2, is safe and significantly prolongs the survival of chemotherapy-refractory gastric cancer patients. This retrospective study evaluated the safety and efficacy of apatinib combined with concurrent brain radiotherapy in NSCLC patients with BMs.MethodsThis trial enrolled patients with non-recurrent BM from histologically-confirmed NSCLC without any limits regarding the BM size/quantity. Eligibility criteria were patients 18–75 years old with measurable BM from histologically-confirmed NSCLC (including both newly-diagnosed and previously treated NSCLC) and expected survival time greater than 3 months. Oral apatinib (500 or 250 mg/day) was started within 1 week prior to commencing whole brain radiotherapy with simultaneous integrated boost (WBRT-SIB) and continued until one week after radiotherapy completion. In addition to toxicities, analyzed outcomes included intracranial overall response rate (iORR), intracranial disease control rate (iDCR), intracranial progression free survival (iPFS), and overall survival (OS).ResultsFrom July 2016 to January 2020, 16 patients were enrolled in this retrospective study. After 3 months of brain radiotherapy, the iORR was 75%, the iDCR was 100%, and the brain edema index (EI) was significantly reduced compared to that before brain radiation therapy (4.2 vs. 1.9; P=0.02). The median iPFS was 16.5 months [95% confidence interval (CI): 15.1–37.4 months]. The median OS was 26 months (95% CI: 17.0–54.0 months). Most of the patients tolerated apatinib well, but 7 patients had side effects, most commonly grade 1 or 2. Only 2 patients experienced grade 3 adverse events (hypertension and oral mucositis), and no grade 4 or 5 toxicities were observed.ConclusionsApatinib combined with WBRT-SIB appears to be safe and effective in treating BMs in NSCLC patients.

A multicenter, open-label phase II trial of second-line apatinib plus irinotecan in patients with advanced gastric cancer.

287 Background: The best choice of second-line chemotherapy regimen for patients with advanced gastric cancer is still debated. Anti-VEGF target therapy is proven to be effective both in second and third line settings. Apatinib, a highly selective VEGFR2 inhibitor, has been demonstrated to be efficacious and well-tolerated for third line of treatment in gastric cancer. The aim of this study is to evaluate the safety and efficacy of apatinib in combination with irinotecan in the second line treatment of advanced gastric cancer. Methods: With the expectation of improving PFS to 4.4m, this investigator-initiated, single arm, multi-center, registered phase II prospective study was designed to enroll 62 eligible patients diagnosed with advanced gastric cancer. Each participant was expected to receive chemotherapy plus apatinib (irinotecan 1800mg/m2, d1, Q2W; apatinib 500mg po qd). The severity of side effects was established according to Common Terminology Criteria for Adverse Events (CTCAE),Version 4.0. Efficacy assessed every three cycles (6 weeks) during the study. The primary endpoint was PFS. The secondary endpoint was OS, ORR, and DCR. The tumor response was determined according to RECIST 1.1 criteria. Results: Baseline characteristics (FAS population): From March 2019 to April 2021, 31 patients from 4 centers in Guangdong province were enrolled. Among them, 28 are eligible for analysis. There are 16 females and 15 males, median age 55 years old. Safety: 82.4% patients reported adverse events (AEs). The incidence of grade 3-4 AEs was 52.9%. Main 3-4 AEs were neutropenia (32.4%), leucopenia (17.6%), anorexia (8.8%), hypoalbuminaemia (8.8%), thrombocytopenia (5.9%), nausea (5.9%). Efficacy: By Aug 31th, 2021, 28 patients were evaluable for response and survival, 1 of them achieved complete response (CR), 10 of them achieved partial response (PR), 8 achieved stable disease (SD), and 9 experienced progression disease (PD). The ORR is 35.48%, the DCR is 61.29%. Median PFS is 4.40m, median OS is 6.64m. Conclusions: Adding apatinib to irinotecan chemotherapy as the second line treatment would be well tolerant in patients with advanced gastric cancer. This indicated the combination could be a potential treatment option for patients with advanced gastric cancer. Clinical trial information: ChiCTR1900021377.

Efficacy of apatinib combined with FOLFIRI in the first-line treatment of patients with metastatic colorectal cancer

SummaryObjective. To evaluate the efficacy and safety of apatinib combined with FOLFIRI in the first-line treatment of advanced metastatic colorectal cancer (mCRC) and explore potential factors of efficacy. Methods. Twenty mCRC patients treated at Affiliated Cancer Hospital of Shanxi Medical University from March 2017 to March 2019 were included according to the enrolment criteria. They provided informed consent and were treated with apatinib combined with FOLFIRI according to the scheduled regimen until disease progression or unacceptable toxicity occurred. The primary endpoint was OS. The secondary endpoints included PFS, ORR, DCRand safety. OS and PFS were calculated using Kaplan–Meier curves. Univariate and multivariate Cox regression analyses were used to evaluate independent prognostic factors of OS and PFS. R was used to determine cut-off values for biochemical indicators. Forest maps were drawn for Cox univariate results and the relationships between NLR and ECOG, which were significant in univariate analysis, and OS were represented by Kaplan–Meier curves. Results. The median OS and PFS were 16.135 months (95% CI: 9.211–22.929) and 6 months (95% CI: 5.425–6.525). Multivariate Cox analysis showed that NLR and CEA were independent prognostic factors. The most common grade 3–4 adverse events were hypertension, diarrhoea, increased alkaline phosphatase, decreased leukocytes and decreased neutrophils. Conclusion. Apatinib combined with FOLFIRI for the first-line treatment of advanced unresectable mCRC showed good efficacy and safety. The baseline NLR was predictive of efficacy, and a low baseline NLR (HR: 0.2895, P = 0.0084) was associated with improved OS.Clinical Research Registration Number: ChiCTR1800015308.

Apatinib plus 5-fluorouracil as a third or subsequent-line treatment option for metastatic colorectal cancer: a phase-II, single-arm, prospective study.

BackgroundFor metastatic colorectal cancer (mCRC) patients for whom at least 2 lines of previous standard therapies have failed, the prognosis is often unfavorable due to very limited subsequent treatment options. We sought to explore the efficacy of apatinib, an oral small-molecule vascular endothelial growth factor receptor-2 inhibitor, plus 5-fluorouracil (5-FU) as a third- or subsequent-line treatment for mCRC.MethodsIn this phase-II, single-arm, prospective study, the eligible patients had been histologically confirmed to have adenocarcinoma of the colon or rectum for which at least 2 previous regimens of standard therapies had failed. All the patients were treated with a daily dose of 250 mg of apatinib, in combination with capecitabine, Tegafur Gimeracil Oteracil Potassium Capsule (S-1), or 5-FU, until disease progression, unacceptable toxicity, or consent withdrawal.ResultsFrom June 2017 to April 2018, 16 patients were enrolled in this study. Among them, 4 achieved partial response, 7 had stable disease, and 5 had progression disease, resulting in an objective response rate of 25.00% [95% confidence interval (CI): 7.27–52.38%], and a disease control rate of 68.75% (95% CI: 41.34–88.98%). The median progression-free survival (PFS) was 4.83 months (95% CI: 2.17–8.90 months), and the median overall survival (OS) was 9.10 months (95% CI: 5.59–15.18 months). The common treatment-related adverse events (AEs) were hand-foot syndrome (56.25%), hypertension (37.50%), proteinuria (37.50%), gingival bleeding (18.75%) and abdominal pain (18.75%). Grade 3 AEs, including hand-foot syndrome (18.75%), hypertension (12.50%), and proteinuria (12.50%), were observed in 7 patients.ConclusionsThe combination regimen of apatinib plus 5-FU had encouraging anti-tumor efficacy, and is a feasible third- or subsequent-line treatment option for mCRC.Trial RegistrationClinicalTrials.gov Identifier: NCT03210064.

Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine–Refractory Differentiated Thyroid Cancer

Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) have a poor prognosis and limited treatment options. To assess the efficacy and safety of apatinib, a highly selective vascular endothelial growth factor (VEGFR-2) inhibitor, in patients with progressive locally advanced or metastatic RAIR-DTC. This randomized, double-blind, placebo-controlled, phase 3 trial (Efficacy of Apatinib in Radioactive Iodine-refractory Differentiated Thyroid Cancer [REALITY]) was conducted in 92 patients with progressive locally advanced or metastatic RAIR-DTC between February 17, 2017, and March 2, 2020, at 21 sites within China, and the data cutoff date for this analysis was March 25, 2020. Patients were randomly assigned (1:1) to apatinib, 500 mg/d, or placebo. Patients who developed progression while receiving placebo were allowed to cross over to apatinib. The primary end point was investigator-assessed progression-free survival (PFS). Secondary end points included overall survival, objective response rate (ORR), disease control rate (DCR), duration of response, time to objective response, and safety. Intention-to-treat analyses were performed to evaluate efficacy. Of the 92 patients included in the trial, 56 were women (60.9%); mean (SD) age at baseline was 55.7 (10.6) years. Patients were randomized to the apatinib (n = 46) or placebo (n = 46) group. The median follow-up duration was 18.1 (IQR, 12.7-22.2) months. The median PFS was 22.2 (95% CI, 10.91-not reached) months for apatinib vs 4.5 (95% CI, 1.94-9.17) months for placebo (hazard ratio, 0.26; 95% CI, 0.14-0.47; P < .001). The confirmed ORR was 54.3% (95% CI, 39.0%-69.1%) and the DCR was 95.7% (95% CI, 85.2%-99.5%) in the apatinib group vs an ORR of 2.2% (95% CI, 0.1%-11.5%) and DCR of 58.7% (95% CI, 43.2%-73.0%) in the placebo group. The median overall survival was not reached for apatinib (95% CI, 26.25-not reached) and was 29.9 months (95% CI, 18.96-not reached) for placebo (hazard ratio, 0.42; 95% CI, 0.18-0.97; P = .04). The most common grade 3 or higher-level treatment-related adverse events in the apatinib group were hypertension (16 [34.8%]), hand-foot syndrome (8 [17.4%]), proteinuria (7 [15.2%]), and diarrhea (7 [15.2%])-none of which occurred in the placebo group. The REALITY trial met its primary end point of PFS at the prespecified interim analysis. Apatinib showed significant clinical benefits in both prolonged PFS and overall survival with a manageable safety profile in patients with progressive locally advanced or metastatic RAIR-DTC. ClinicalTrials.gov Identifier: NCT03048877.

Clinical Experience with Apatinib and Camrelizumab in Advance Clear Cell Sarcoma: A Retrospective Study.

PurposeAdvanced clear cell sarcoma (CCS) is a rare subtype of sarcoma with few effective treatments. Evidence shows that apatinib is efficacious and safe for CCS. This study aimed to assess the safety and efficacy of apatinib and/or camrelizumab (a PD-1 inhibitor) in treating advanced CCS.MethodsWe retrospectively reviewed 12 patients with advanced CCS who received apatinib and/or camrelizumab therapy between November 2018 and July 2021. Standard descriptive statistics were employed for continuous variables and categorical variables (number and percentage).ResultsOf the 12 CCS patients, 3 had a partial response (PR), and 4 had stable disease (SD). Among the 5 patients treated with apatinib monotherapy, 1 PR and 2 SD were found, and the addition or replacement of camrelizumab after progressive disease (PD) did not work. In the 4 patients who received apatinib plus camrelizumab combination therapy, 1 PR and 1 SD were found. All 3 patients who received camrelizumab first had PD, and 1 PR and 1 SD were found after adding apatinib. Grade 3 or 4 adverse events were significantly more common in the apatinib plus camrelizumab combination therapy than in the apatinib or camrelizumab monotherapy, and these included increased aspartate aminotransferase and increased alanine aminotransferase levels.ConclusionApatinib has promising effectiveness for CCS. Camrelizumab efficacy for the treatment of clear cell sarcoma is inconclusive. The efficacy of apatinib and PD-1 inhibitors in CCS need to be further investigated in prospective clinical trials.

Investigation of the Clinical Efficacy of Apatinib Combined With SOX in the Treatment of Advanced Gastric Cancer

Investigation of the Clinical Efficacy of Apatinib Combined With SOX in the Treatment of Advanced Gastric Cancer

Efficacy and Response Biomarkers of Apatinib in the Treatment of Malignancies in China: A Review.

Apatinib is a multitarget tyrosine kinase inhibitor marketed in China for the treatment of advanced gastric cancer (GC) and hepatocellular carcinoma (HCC). It has also been used off-label for the treatment of many other malignancies. To comprehensively evaluate the efficacy of apatinib as a targeted therapy in the treatment of malignancies, we conducted systematic online and manual searches of the literature on apatinib in the treatment of malignancies. In this review, we first summarized the efficacy of apatinib against various malignancies based on clinical trials where results have been reported. In prospectively registered trials, apatinib has been proven to be effective against GC, HCC, lung cancer, breast cancer, sarcoma, esophageal cancer, colorectal cancer, ovarian cancer, cervical cancer, cholangiocarcinoma, diffuse large B-cell lymphoma, nasopharyngeal carcinoma, and differentiated thyroid cancer. The response biomarkers for apatinib were also reviewed. This review will serve as a good reference for the application of apatinib in clinical studies and the design of clinical trials.

370P Prospective study of apatinib combined with whole brain radiation therapy and simultaneous integrated boost for brain metastases from lung cancer

Brain metastases (BM) develop during the disease course in 20-65% of lung cancer patients. As neo-angiogenesis is crucial to BM growth, the combination of angiogenesis inhibitors and brain radiotherapy is an active focus of research. Apatinib, a tyrosine kinase inhibitor that selectively inhibits the vascular endothelial growth factor receptor-2, is safe and significantly prolongs survival in chemotherapy-refractory gastric cancer. This prospective study evaluated the safety and efficacy of apatinib combined with concurrent whole brain radiation therapy (WBRT) in lung cancer patients with BM.

Apatinib inhibits cell proliferation and migration of osteosarcoma via activating LINC00261/miR-620/PTEN axis

ABSTRACT Apatinib has been recently identified as a potential treatment option for osteosarcoma (OS). Nonetheless, the molecular mechanism of Apatinib in regulating OS progression remains unclear. To explore the downstream molecules that mediated the tumor-suppressive effect of Apatinib on OS. Expression levels of genes were detected by RT-qPCR and western blot assays. Functional assays including Transwell assay were applied to detect the proliferation, apoptosis and migration of OS cells. Molecular interactions were detected by luciferase reporter assay and RIP assay. Apatinib inhibited the proliferation and migration of OS cells. LINC00261 was down-regulated in OS cells but then up-regulated after the treatment by Apatinib. Silencing LINC00261 abrogated the suppressive effect of Apatinib on OS cell proliferation and migration. MicroRNA-620 (miR-620) could be sponged by LINC00261. Besides, miR-620 was up-regulated in OS cells and Apatinib treatment reduced miR-620 expression. Furthermore, LINC00261 acted as a competitive endogenous RNA (ceRNA) by sequestering miR-620 to up-regulate the expression of phosphatase and tensin homolog (PTEN). Moreover, Apatinib hindered in vitro cell proliferation and migration as well as the in vivo tumorigenesis of OS through LINC00261/miR-620/PTEN axis. Apatinib-enhanced LINC00261 restrained OS via miR-620/PTEN axis, indicating LINC00261 might promote the efficacy of Apatinib on OS.