An open-label, single-arm, prospective study of TACE combined with apatinib for unresectable liver metastases from colorectal cancer
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ABSTRACT:
DISEASE(S): Colorectal Liver Metastases
PROVIDER: 2671010 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:ObjectiveTo evaluate the efficacy and safety of sintilimab combined with apatinib plus capecitabine in the treatment of unresectable hepatocellular carcinoma (HCC) to provide a more effective first-line treatment for patients with advanced HCC.MethodsThis open-label, prospective, phase II study included patients with unresectable HCC who did not receive systematic treatment. The patients were treated with sintilimab (200 mg, intravenous drip, once every 3 weeks) combined with apatinib (250 mg, oral administration, once a day) plus capecitabine (1000 mg/m2, twice a day; after 2 weeks of oral administration, the drug was stopped for 1 week; course of treatment, 3 weeks). The primary endpoint was the objective response rate (ORR). The secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety.ResultsForty-seven patients (1 lost to follow-up) were enrolled in the study. As of March 1, 2022, the ORR and DCR were 50.0% (95% CI: 34.9-65.1%) and 91.3% (95% CI: 79.2-97.6%), respectively, after blind, independent imaging evaluation. The median follow-up time was 18.7 months (95% CI: 17.2-20.2 months). The median PFS was 9.0 months (95% CI: 7.1-10.9 months). The median DoR was 10.8 months (95% CI: 4.8-16.8 months). The median OS was not reached, and the 1-year OS rate was 71.7% (95% CI: 56.5-84.0%). Only 28.3% (13/46) of patients had grade 3/4 treatment-related adverse events.ConclusionSintilimab combined with apatinib plus capecitabine has good safety and anti-tumor activity as a first-line treatment for unresectable HCC. This is worthy of further multi-center, prospective, randomized, large-sample clinical studies.Clinical trial registrationhttps://ClinicalTrials.gov, identifier NCT04411706.
| S-EPMC9459134 | biostudies-literature
Project description:Lessons learnedPatient compliance with the oral dosage treatment was good, with no need for hospitalization. Patients with tracheal and esophageal fistulas can take crushed apatinib by nutrient tube, with the same bioavailability and efficacy. Apatinib may be an effective and safe second- or further-line treatment for advanced esophageal cancer.BackgroundApatinib is an inhibitor of vascular endothelial growth factor receptor-2 (VEGFR2), which is thought to play a role in esophageal cancer progression. Our goal was to evaluate the efficacy and safety of apatinib in patients with unresectable esophageal cancer and to examine whether VEGFR2 expression influenced the clinical response.MethodsThis single-arm, open-label, investigator-initiated phase II study enrolled patients with advanced squamous cell carcinoma (SCC) or adenocarcinoma of the esophagus or esophagogastric junction who were admitted to Tianjin Medical University Cancer Institute and Hospital between August 2017 and January 2019. Apatinib monotherapy (500 mg/day) was given orally or via an enteral tube until disease progression, unacceptable toxicity, withdrawal, or death. Patients were followed until treatment was discontinued or death. The main endpoints were tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs).ResultsAmong 32 patients screened for inclusion, 30 were included in the safety and survival analyses (i.e., received apatinib), and 26 were included in the efficacy analysis (at least one imaging follow-up). Median follow-up time and exposure to apatinib were 5.34 months and 72 days, respectively. Among 26 patients included in the efficacy analysis, 2 had a partial response (PR; 7.7%) and 14 had stable disease (SD; 53.8%). The overall response rate (ORR) was 7.7%, and the disease control rate (DCR) was 61.5%. Median PFS and OS were 4.63 months (95% confidence interval, 2.11-7.16 months) and 6.57 months (4.90 months to not estimable), respectively. Fifteen patients (50.0%) experienced treatment-related AEs, most commonly hypertension (26.7%), diarrhea (20.0%), and hand-foot-skin reaction (10.0%). No patients had grade ≥4 treatment-related AEs.ConclusionApatinib was effective as second- or further-line treatment for advanced esophageal cancer.
| S-EPMC7543358 | biostudies-literature
Project description:BackgroundThe prognosis for esophageal cancer (EC), a common malignant tumor, is poor. The new oral small-molecule tyrosine kinase inhibitor apatinib has shown an excellent therapeutic effect on treating EC. Camrelizumab is a humanized programmed death 1 (PD-1) inhibitor with high affinity. Immune checkpoint inhibitors combined with chemotherapy have become the standard first-line treatment for advanced EC. The new combination strategy of anti-angiogenic therapy combined with immunotherapy has great application prospects in the treatment of tumors. We aimed to assess camrelizumab in combination with apatinib as a new combination regimen for advanced or metastatic esophageal squamous cell carcinoma (ESCC).MethodsIn this study, we recruited patients with an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, with pathologically confirmed unresectable, locally advanced, locally recurrent, or metastatic ESCC. Each patient received an intravenous infusion of camrelizumab 200 mg and oral administration of apatinib 250 mg once a day, every 21 days, as a cycle until disease progression, intolerance, or death. The primary endpoint was the objective response rate (ORR), while the Kaplan-Meier method and LIFETEST procedure were used to estimate survival functions for overall survival (OS) and progression-free survival (PFS). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used to evaluate adverse events.ResultsBetween December 1, 2019 and July 31, 2022, 35 patients were enrolled, with 29 patients in the efficacy and safety analysis. The ORR was 34.5%, and the disease control rate (DCR) reached 82.8%. Median OS was 13.8 months (95% CI: 11.2-16.2), and the estimated 6-, 9-, and 12-month OS rates were 85.5% (95% CI: 65.7-94.3%), 80.9% (95% CI: 60.3-91.5%), and 67.0% (95% CI: 43.8-82.4%), respectively. Median PFS was 9.5 months (95% CI: 7.0-13.6). The most prominent grade ≥3 adverse events associated with treatments were alanine aminotransferase (ALT) increase (10.3%), hypertension (10.3%), and reactive cutaneous capillary endothelial proliferation (CCEP) (6.9%), and no deaths occurred due to adverse events.ConclusionsAmong patients with advanced or metastatic ESCC, camrelizumab combined with apatinib showed a reasonable remission rate and survival benefit with a manageable safety profile.
| S-EPMC10932671 | biostudies-literature
Project description:Interventions: Case series:TACE combined with apatinib
Primary outcome(s): time to progression
Study Design: Non randomized control
| 2677541 | ecrin-mdr-crc
Project description:PurposeTreatment options for relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) represent an unmet medical need. Apatinib is a new oral tyrosine kinase inhibitor mainly targeting vascular endothelial growth factor receptor-2 (VEGFR-2) to inhibit tumour angiogenesis. In the present study, we evaluated the efficacy and safety of apatinib for patients with RR DLBCL.Patients and methodsIn this phase II, open-label, single-arm, prospective study, we enrolled patients aged 14-70 years with treatment failure of at least two chemotherapeutic regimens using Simon's two-stage design. All patients were administered apatinib at an initial dose of 500 mg on a 4-week cycle at home and visited the outpatient clinic every two cycles to evaluate efficacy and to record adverse events. We considered objective response rate (ORR) as the primary end point, and progression-free survival (PFS), and overall survival (OS) plus duration of response (DoR) as the secondary end point. (This trial was registered at ClinicalTrials.gov, identifier: NCT03376958.).ResultsFrom January 2017 to February 2019, we screened 35 patients and enrolled 32 eligible patients. At the cutoff point (April 2019), we noted 2 (6.3%) complete responses, 12 (37.5%) partial responses, and 9 (28.1%) stable diseases, attributing to an ORR of 43.8% and a disease control rate of 71.9%. The median PFS and OS were 6.9 (95% confidence interval [CI], 5.8-7.9) and 7.9 months (95% CI, 7.0-8.7), respectively. The median DoR was 5.0 months (95% CI, 3.5-6.5) for patients who achieved PR. The most common grade 3-4 adverse events (AE) were hypertension (12.6%), hand-foot syndrome (9.4%), and leucopenia (6.3%). No apatinib-related deaths were noted.ConclusionHome administration of apatinib shows promising efficacy and manageable AEs in patients with RR DLBCL.
| S-EPMC6986930 | biostudies-literature
Project description:In the REGONIVO study, regorafenib combined with nivolumab was effective in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC), which indicated anti-angiogenic drugs may enhance the efficacy of immune checkpoint inhibitors. Therefore, we designed a single-arm, single-center, open-label, phase II trial to determine the toxicity and efficacy of SHR-1210 (an anti-PD-1 antibody) plus apatinib in MSS mCRC. The sample size was estimated using a Simon Optimum two-stage design. 10 patients were included at the first stage and if one effective patient observed, an additional 19 patients would be added. Patients with MSS mCRC who refractory to second-line treatment or intolerant to standard treatment were given SHR-1210 200 mg every 2 weeks and apatinib 250-375 mg once daily until unacceptable toxicity or disease progression occurred. In our study, the objective response rate was 0% and the disease control rate was 22.2%. The median progression-free survival was 1.83 months (95% confidence interval (CI) 1.80-1.86 months), and the median overall survival was 7.80 months (95% CI 0-17.07). Treatment-related adverse events (AEs) occurred in all patients (100%). The most common treatment-related AEs were hypertension and proteinuria (70% each). Grade 3 AEs were observed in nine patients (9/10, 90%), and the commonest was hypertension (30%). In conclusion, SHR-1210 combined with apatinib has failed to improve the efficacy of treatment of MSS mCRC, and the intolerable toxicity may be the leading cause.
| S-EPMC7539766 | biostudies-literature
Project description:Interventions: single arm:camrelizumab combined with apatinib mesylate
Primary outcome(s): PFS
Study Design: Single arm
| 2690370 | ecrin-mdr-crc
Project description:Purpose: Primary retroperitoneal liposarcomas (RLPSs) are rare heterogeneous tumors for which there are few effective therapies. Certain anti-angiogenic tyrosine kinase inhibitors have demonstrated efficacy against various solid tumors. The aims of this study were to investigate the effect of Apatinib against retroperitoneal liposarcoma cells and its underlying mechanism and to explore the anti-tumor efficacy of a combination of Apatinib and Epirubicin. Methods: SW872 cells were treated with Apatinib(18μM) for 24 h. The RNAs of the control group and experimental group were stored in TRIzol reagent at -80 ℃. Then mRNA extraction and RNA sequencing were performed by Beijing Mygenostics Co. Ltd., Beijing, China. A Bioanalyzer 2100 System (Agilent Technologies, Santa Clara, CA, USA) was used to assay RNA integrity. An AMPureXP system (BeckmanCoulter, Brea, CA, USA) was used to perform PCR on the products. Quality-tested library preparations were sequenced on the Illumina Novaseq platform (Illumina, San Diego, CA, USA). There were three biological replicates per condition. Differential expression analysis of both groups was performed using DESeq2R v. 1.20.0. The Benjamini-Hochberg multiple hypothesis test correction was performed to obtain the false discovery rate (FDR). The criteria used to select the DEGs were |log2(FoldChange)| > 0.5 and FDR < 0.05. When log2(FoldChange) > 0, the gene was considered upregulated. When log2(FoldChange) < 0, the gene was considered downregulated. profiler package in R (R Core Team, Vienna, Austria) was used for GO function and KEGG pathway enrichment analyses of the DEGs. Histograms and bubble graphs were plotted with the ggplot2 package in R v. 3.4.3. Results:To elucidate the mechanisms by which Apatinib inhibited liposarcoma cells, we used RNA-seq to evaluate relative genetic changes in the SW872 cells after being treated with Apatinib for 24 hs, and found 2,038 DEGs, including 1,059 significantly downregulated genes and 979 significantly upregulated genes. The output of the KEGG pathway enrichment analysis suggests that Apatinib might inhibit SW872 cell proliferation through p53, DNA replication, and other important signaling pathways. GO enrichment analysis was performed on the genes that were significantly altered after Apatinib application.High-throughput RNA sequencing showed that Apatinib downregulated the expression of TYMS and RRM2. Conclusions: Apatinib showed strong efficacy against liposarcoma both in vitro and in vivo. Apatinib might inhibit liposarcoma cell proliferation through the RRM2/PI3K/AKT/mTOR signaling pathway and downregulate PD-L1 via the TYMS/STAT3 signaling pathway.
2021-11-03 | GSE185783 | GEO
Project description:PurposeCamrelizumab is an antibody against programmed death protein 1. We assessed the activity and safety of camrelizumab plus apatinib, a tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2, in patients with advanced cervical cancer.MethodsThis multicenter, open-label, single-arm, phase II study enrolled patients with advanced cervical cancer who progressed after at least one line of systemic therapy. Patients received camrelizumab 200 mg every 2 weeks and apatinib 250 mg once per day. The primary end point was objective response rate (ORR) assessed by investigators per RECIST version 1.1. Key secondary end points were progression-free survival (PFS), overall survival (OS), duration of response, and safety.ResultsForty-five patients were enrolled and received treatment. Median age was 51.0 years (range, 33-67 years), and 57.8% of patients had previously received two or more lines of chemotherapy for recurrent or metastatic disease. Ten patients (22.2%) had received bevacizumab. Median follow-up was 11.3 months (range, 1.0-15.5 months). ORR was 55.6% (95% CI, 40.0% to 70.4%), with two complete and 23 partial responses. Median PFS was 8.8 months (95% CI, 5.6 months to not estimable). Median duration of response and median OS were not reached. Treatment-related grade 3 or 4 adverse events (AEs) occurred in 71.1% of patients, and the most common AEs were hypertension (24.4%), anemia (20.0%), and fatigue (15.6%). The most common potential immune-related AEs included grade 1-2 hypothyroidism (22.2%) and reactive cutaneous capillary endothelial proliferation (8.9%).ConclusionCamrelizumab plus apatinib had promising antitumor activity and manageable toxicities in patients with advanced cervical cancer. Larger randomized controlled trials are warranted to validate our findings.
| S-EPMC7768345 | biostudies-literature
Project description:PurposeImmune checkpoint inhibitors combined with antiangiogenic therapy reportedly have potential synergistic antitumor activity. We investigated the activity and safety of this regimen for recurrent/metastatic nasopharyngeal carcinoma (NPC).MethodsThis single-arm, Simon two-stage study enrolled patients with recurrent/metastatic NPC who were refractory to at least first-line systemic therapy and treatment-naive to immune checkpoint inhibitors. The patients received camrelizumab 200 mg once every 3 weeks and apatinib 250 mg once per day. The primary end point was the objective response rate. Key secondary end points included disease control rate, progression-free survival, duration of response, overall survival, and safety.ResultsBetween October 14, 2020, and December 23, 2021, 58 patients were enrolled, and all were included in the efficacy and safety analysis set. The objective response rate was 65.5% (95% CI, 51.9 to 77.5), and the disease control rate was 86.2% (95% CI, 74.6 to 93.9). The median duration of response was not reached, and the median progression-free survival was 10.4 months (95% CI, 7.2 to 13.6), with a median follow-up duration of 12.4 months (range, 2.1-19.9 months). Treatment-related adverse events (TRAEs) of grade 3 or higher were reported in 34 (58.6%) patients, with the most common being hypertension (19.0%), nasopharyngeal necrosis (15.5%), headache (12.1%), AST elevation (10.3%), and creatine phosphokinase elevation (10.3%). Sixteen (27.6%) patients discontinued apatinib treatment before progression because of unbearable TRAEs, and the most common complication was nasopharyngeal necrosis (9/16; 56.3%). Recurrent nasopharyngeal lesions (odds ratio, 5.94 [95% CI, 1.45 to 24.24]) and reirradiation (odds ratio, 5.33 [95% CI, 1.15 to 24.79]) were significantly positively correlated with nasopharyngeal necrosis.ConclusionCamrelizumab plus apatinib had promising antitumor activity in patients with refractory recurrent/metastatic NPC who failed first-line therapy. Moderate to severe TRAEs were experienced by 58.6%, including nasopharyngeal necrosis associated with local recurrence and a history of reirradiation.
| S-EPMC10414735 | biostudies-literature