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Apatinib as first-line treatment in patients with advanced hepatocellular carcinoma: a phase II clinical trial.

ABSTRACT: Background:The prognosis for advanced hepatocellular carcinoma (HCC) remains clinically unsatisfying. Apatinib has proven to be a very effective treatment for advanced HCC in our previous retrospective study. Our aim in this study was to evaluate the efficacy, safety, and toxicity of apatinib in patients with advanced HCC. Methods:This single-arm, open-label phase II clinical trial enrolled patients with advanced HCC. These patients received apatinib, 500 mg once daily, until disease progression, unacceptable toxicity, consent withdrawal, or death. One treatment cycle consisted of 4 weeks of apatinib treatment. The response evaluation criteria in solid tumors (RECIST) was used to assess tumor response every 1-2 cycles. The primary endpoint was the objective response rate (ORR), while the secondary endpoints were the overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and toxicity. Results:Between December 2016 and June 2018, 23 patients were enrolled in the study, 22 of whom were available for response evaluation. The cutoff date was August 10, 2018. The overall ORR and DCR were 30.4% and 65.2%, respectively. The median OS and PFS were 13.8 (95% CI: 5.3-22.3) and 8.7 (95% CI: 5.9-11.1) months, respectively. The most common treatment-related adverse events were proteinuria (39.1%), hypertension (34.8%), and hand-foot-skin reaction (34.8%). Conclusions:Apatinib showed robust clinical activity in patients with advanced HCC. Moreover, apatinib was safe to use, well tolerated, and had acceptable toxicity. (NCT03046979).

SUBMITTER: Hou Z

PROVIDER: S-EPMC7576000 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Apatinib as first-line treatment in patients with advanced hepatocellular carcinoma: a phase II clinical trial.

Hou Zhenyu Z Zhu Keyun K Yang Xuejiao X Chen Ping P Zhang Wei W Cui Yunlong Y Zhu Xiaolin X Song Tianqiang T Li Qiang Q Li Huikai H Zhang Ti T

Annals of translational medicine 20200901 17

<h4>Background</h4>The prognosis for advanced hepatocellular carcinoma (HCC) remains clinically unsatisfying. Apatinib has proven to be a very effective treatment for advanced HCC in our previous retrospective study. Our aim in this study was to evaluate the efficacy, safety, and toxicity of apatinib in patients with advanced HCC.<h4>Methods</h4>This single-arm, open-label phase II clinical trial enrolled patients with advanced HCC. These patients received apatinib, 500 mg once daily, until dise ...[more]

PMID: 33145266

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Project description:BackgroundEffective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma (ESCC). The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects. Therefore, we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.MethodsIn this single-arm prospective phase II trial, patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg, liposomal paclitaxel 150 mg/m2 , and nedaplatin 50 mg/m2 on day 1, and apatinib 250 mg on days 1-14. The treatments were repeated every 14 days for up to 9 cycles, followed by maintenance therapy with camrelizumab and apatinib. The primary endpoint was objective response rate (ORR) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.ResultsWe enrolled 30 patients between August 7, 2018 and February 23, 2019. The median follow-up was 24.98 months (95% confidence interval [CI]: 23.05-26.16 months). The centrally assessed ORR was 80.0% (95% CI: 61.4%-92.3%), with a median duration of response of 9.77 months (range: 1.54 to 24.82+ months). The DCR reached 96.7% (95% CI: 82.8%-99.9%). The median PFS was 6.85 months (95% CI: 4.46-14.20 months), and the median OS was 19.43 months (95% CI: 9.93 months - not reached). The most common grade 3-4 treatment-related adverse events (AEs) were leukopenia (83.3%), neutropenia (60.0%), and increased aspartate aminotransferase level (26.7%). Treatment-related serious AEs included febrile neutropenia, leukopenia, and anorexia in one patient (3.3%), and single cases of increased blood bilirubin level (3.3%) and toxic epidermal necrolysis (3.3%). No treatment-related deaths occurred.ConclusionsCamrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC. Randomized trials to evaluate this new combination strategy are warranted.Trial registrationThis trial was registered on July 27, 2018, at ClinicalTrials.gov (identifier: NCT03603756).

Project description:Lessons learnedTrebananib leveraging anti-angiogenic mechanism that is distinct from the classic sorafenib anti-vascular endothelial growth factor inhibition did not demonstrate improved progression-free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang-2 levels' association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang-2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang-2.BackgroundAng-1 and Ang-2 are angiopoietins thought to promote neovascularization via activation of the Tie-2 angiopoietin receptor. Trebananib sequesters Ang-1 and Ang-2, preventing interaction with the Tie-2 receptor. Trebananib plus sorafenib combination has acceptable toxicity. Elevated Ang-2 levels are associated with poor prognosis in hepatocellular carcinoma (HCC).MethodsPatients with HCC, Eastern Cooperative Oncology Group ≤2, and Childs-Pugh A received IV trebananib at 10 mg/kg or 15 mg/kg weekly plus sorafenib 400 mg orally twice daily. The study was planned for ≥78% progression-free survival (PFS) rate at 4 months relative to 62% for sorafenib historical control (power = 80% α = 0.20). Secondary endpoints included safety, tolerability, overall survival (OS), and multiple biomarkers, including serum Ang-2.ResultsThirty patients were enrolled sequentially in each of the two nonrandomized cohorts. Demographics were comparable between the two arms and the historical controls. PFS rates at 4 months were 57% and 54% on the 10 mg/kg and 15 mg/kg trebananib cohorts, respectively. Median OS was 17 and 11 months, respectively. Grade 3 and above events noted in ≥10% of patients included fatigue, hypertension, diarrhea, liver failure, palmar-plantar erythrodysesthesia syndrome, dyspnea, and hypophosphatemia. One death was due to hepatic failure. Serum Ang-2 dichotomized at the median was associated with improved OS in both cohorts.ConclusionThere was no improvement in PFS rate at 4 months in either cohort, when compared with sorafenib historical control.

Project description:Lessons learnedApatinib combined with S-1 was not superior to other chemotherapy regimens as first-line therapy for advanced gastric cancer. There was a tendency for patients with lymph node metastasis to have prolonged median progression-free survival and median overall survival, compared with patients with liver metastasis.BackgroundThe best choice of first-line chemotherapy regimen for patients with metastatic gastric cancer is still debated. We combined apatinib and S-1 as a new first-line therapy to treat advanced gastric cancer. The efficacy and safety of the combination were assessed, with the goal of determining the most appropriate subgroup of patients who could benefit from this new regimen.MethodsThis study was an open, exploratory single-arm, phase II trial. Enrolled patients received apatinib plus S-1 treatment (apatinib, 500 mg, once a day [qd], days 1-21; S-1, 40 mg/m2 , bid, days 1-14). The primary endpoints were progression-free survival (PFS) and safety of this new regimen. Next-generation sequencing was used to explore potential biomarkers.ResultsA total of 30 patients were enrolled. The median progression-free survival (mPFS) was 4.21 months (95% confidence interval [CI], 2.29-6.13 months). The median overall survival (mOS) was 7.49 months (95% CI, 4.81-10.17 months). Patients with lymph node metastasis had prolonged mPFS and mOS when compared with those with liver metastasis (mPFS, 4.21 vs. 1.84 months; mOS, 8.21 vs. 6.31 months, p = .08). The most common grade 3 to 4 adverse events were abdominal pain, dizziness, and diarrhea. Gene mutation profiles between the two subgroups were significantly different.ConclusionApatinib combined with S-1 was not superior to other chemotherapy regimens as first-line therapy for advanced gastric cancer. Toxicity was consistent with known profiles when given as monotherapy. There was a tendency toward prolonged mPFS and mOS in patients with lymph node metastasis compared with patients with liver metastasis, which could support the need to design a future clinical trial with a better defined patient population.

Dataset Information

Apatinib as first-line treatment in patients with advanced hepatocellular carcinoma: a phase II clinical trial.

Publications

Apatinib as first-line treatment in patients with advanced hepatocellular carcinoma: a phase II clinical trial.

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