Dataset Information

Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer.

ABSTRACT:

Background

Alpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting.

Methods

From September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastatic gastric cancer, were enrolled to perform this analysis. Patients received oral apatinib as monotherapy or combination therapy. A treatment cycle was defined as 28 days. The primary outcome was progression-free survival (PFS) and overall survival (OS), and the secondary outcomes included safety, objective response rate (ORR), and disease control rate (DCR).

Results

Twenty patients were evaluated for the apatinib efficacy analysis. The ORR of apatinib was 10%, whereas the DCR was 70%. The median PFS was 3.5 months [95%confidence interval (CI): 2.34-4.66]. The median OS was 4.5 months (95%CI: 3.49-5.51). Median OS of AFPGC patients without carcinoembryonic antigen (CEA) elevation achieved 30.8 months. CEA elevation was considered to be a potential independent predictive factor for OS (P?=?0.030) and PFS (P?=?0.047) by the analysis of multivariate analysis. The most common grade 3 to 4 adverse events (AEs) were hypertension (4.8%), hand-foot syndrome (4.8%), anorexia (4.8%), and vomiting and nausea (4.8%).

Conclusion

Apatinib showed promising efficacy and an acceptable safety profile in patients with advanced AFPGC. Antiangiogenic therapy may be a good strategy for the treatment of AFPGC as a rare sub-type of gastric cancer.

Trial registration

AHEAD-G202 (NCT02668380).

SUBMITTER: Li N

PROVIDER: S-EPMC7777135 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer.

Li Ningning N Bai Chunmei C Zhang Ruixing R Ma Liwen L Ren Xiubao X Zhang Junping J Fu Zhanzhao Z Zhao Lin L

Translational oncology 20201228 2

<h4>Background</h4>Alpha-fetoprotein-producing gastric cancer (AFPGC) poses a therapeutic challenge worldwide because of its poor prognosis. This study aimed to evaluate the efficacy and safety of antiangiogenic drug apatinib in advanced AFPGC in a real-world setting.<h4>Methods</h4>From September 2015 to December 2017, twenty-one patients identified with AFPGC from the clinical trial AHEAD-G202, an open-label, prospective, multicenter, non-interventional study of apatinib for advanced metastati ...[more]

PMID: 33383486

Similar Datasets

Project description:Gastric cancer (GC), one of the types of tumor most prone to malignancy, is characterized by high lethality. Numerous molecular mediators of GC have been identified, including transcription factors, signaling molecules and non-coding RNAs. Recently, inhibition of angiogenesis has emerged as a potential strategy for GC therapy. In the present study, the levels of vascular endothelial growth factor (VEGF), peroxisome proliferator-activated receptor-? (PPAR?) and miR-21 in GC patients and individuals without cancer, and the correlation between VEGF and miR-21, and PPAR? and miR-21 expression were analyzed. In addition, the GC MKN45 cell line was treated with apatinib (a tyrosine kinase inhibitor) and aspirin (an activator of the transcription factor, PPAR?) to investigate the effects of these compounds on tumorigenesis. Furthermore, the present study attempted to elucidate the molecular mechanisms of alteration of GC tumorigenesis by aspirin and apatinib. The results of the current study demonstrated that there was a higher expression of VEGF and miR-21 in GC tissues compared with that in morphologically adjacent normal tissues whereas PPAR? expression was decreased. These results were confirmed in vitro, as treatment of MKN45 cells with VEGF resulted in a significant increase in miR-21 expression and a significant reduction in PPAR? protein expression. Furthermore, the inhibitory effects of VEGF on PPAR? mRNA and protein expression were demonstrated to be mediated by miR-21. Suppression of PPAR? protein expression attenuated the inhibitory effects of miR-21 on the level of PPAR? mRNA, thereby enhancing tumorigenesis in gastric cancer. Treatment of MKN45 cells with aspirin reduced the levels of phosphorylated AKT by activating PPAR?, whereas treatment with apatinib inhibited the phosphorylation of vascular endothelial growth factor receptor 2 and phosphoinositide-3 kinase in MKN45 cells. Finally, treatment of MKN45 cells with apatinib and aspirin suppressed tumorigenesis by inhibiting cell proliferation, migration, invasion and colony formation. Taken together, the results of the present study indicate that treatment with a combination of aspirin and apatinib may be a potential therapeutic strategy for GC treatment.

Project description:ImportanceApatinib is a novel treatment option for chemotherapy-refractory advanced gastric cancer (GC), but it has not been evaluated in patients with locally advanced GC.ObjectiveTo investigate the effectiveness and safety of apatinib combined with S-1 plus oxaliplatin (SOX) as a neoadjuvant treatment for locally advanced GC.Design, setting, and participantsThis multicenter, prospective, single-group, open-label, phase 2 nonrandomized controlled trial was conducted in 10 centers in southern China. Patients with M0 and either clinical T2 to T4 or N+ disease were enrolled between July 1, 2017, and June 30, 2019. Statistical analysis was performed from December 1, 2019, to January 31, 2020.InterventionsEligible patients received apatinib (500 mg orally once daily on days 1 to 21 and discontinued in the last cycle) plus SOX (S-1: 40-60 mg orally twice daily on days 1 to 14; oxaliplatin: 130 mg/m2 intravenously on day 1) every 3 weeks for 2 to 5 cycles. A D2 gastrectomy was performed 2 to 4 weeks after the last cycle.Main outcomes and measuresThe primary end point was R0 resection rate. Secondary end points were the response rate, toxic effects, and surgical outcome.ResultsA total of 48 patients (mean [SD] age, 63.2 [8.2] years; 37 men [77.1%]) were enrolled in this study. Forty patients underwent surgery (38 had gastrectomy, and 2 had exploratory laparotomy), with an R0 resection rate of 75.0% (95% CI, 60.4%-86.4%). The radiologic response rate was 75.0%, and T downstaging was observed in 16 of 44 patients (36.4%). The pathological response rate was 54.2% (95% CI, 39.2%-68.6%); moreover, this rate was significantly higher in patients who achieved a radiologic response compared with those who did not (12 [80.0%] vs 1 [20.0%]; P = .03) and in those who had an Eastern Cooperative Oncology Group Performance Status score of 0 (20 [76.9%] vs 10 [45.5%]; P = .03) or had tumors located in the upper one-third of the stomach (16 [61.5%] vs 7 [31.8%]; P = .04). Patients who achieved a pathological response (vs those who did not) had significantly less blood loss (median [range]: 60 [10-200] mL vs 80 [20-300] mL; P = .04) and significantly more lymph nodes harvested (median [range]: 40 [24-67] vs 32 [19-51]; P = .04) during surgery. Postoperative complications were observed in 7 of 38 patients (18.4%). Grade 3 toxic effects occurred in 16 of 48 patients (33.3%), and no grade 4 toxic effects or preoperative deaths were observed.Conclusions and relevanceThis nonrandomized controlled trial found that apatinib combined with SOX was effective and had an acceptable safety profile as a neoadjuvant treatment for locally advanced GC. A large-scale randomized clinical trial may be needed to confirm the findings.Trial registrationClinicalTrials.gov Identifier: NCT03192735.

Project description:BackgroundLimited data are available for the combination regimen of anti-programmed cell death protein 1 (PD-1) inhibitor and anti-angiogenic agents as second-line therapy for the treatment of patients with advanced non-small cell lung cancer (NSCLC), especially in patients with squamous NSCLC. This study assessed the efficacy and safety of camrelizumab plus apatinib (a vascular endothelial growth factor receptor 2 inhibitor) as second-line treatment in patients with advanced squamous NSCLC.MethodsIn the Cohort 3 from a phase II dose-expansion trial, patients with advanced non-central squamous NSCLC who were immunotherapy naïve and had failed prior first-line platinum-based chemotherapy received 200 mg of camrelizumab intravenously every 2 weeks plus oral apatinib at the recommended dose of 250 mg once daily. The primary endpoint was objective response rate (ORR) assessed by the investigators as per the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1.ResultsCohort 3 was prematurely terminated because of slow accrual after 25 patients with advanced squamous NSCLC had been enrolled between 10 October 2018, and 3 March 2019. At the data cutoff date of 12 June 2020, the median follow-up was 13.3 (range, 1.6 to 19.2) months. Among all 25 participants, the ORR was 32.0% (95% CI: 14.9% to 53.5%), the clinical benefit rate was 44.0% (95% CI: 24.4% to 65.1%), and the disease control rate (DCR) was 84.0% (95% CI: 63.9% to 95.5%). Median progression-free survival (PFS) was 6.0 (95% CI: 3.5 to 8.1) months, and median overall survival (OS) was 13.3 (95% CI: 6.4 to 18.8) months. Furthermore, clinical benefits from this combination regimen were evident across all tumor PD ligand 1 (PD-L1) expression subgroups. The most common treatment-related adverse events (TRAEs) of grade 3 or higher were hypertension (44.0%) and palmar-plantar erythrodysesthesia (16.0%). As reported by the investigators, 3 participants (12.0%) died due to TRAEs (interstitial pneumonia, hemorrhage, and unknown reason; n=1 each, 4%).ConclusionsCamrelizumab plus apatinib as second-line therapy showed satisfactory antitumor activity in patients with non-central squamous NSCLC, regardless of tumor PD-L1 expression. Camrelizumab plus apatinib had a manageable safety profile in this patient population, and the toxic reactions observed were generally consistent with those in previously reported studies. Interstitial pneumonia and hemorrhage are important risks requiring careful monitoring and prompt intervention.

Dataset Information

Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer.

Background

Methods

Results

Conclusion

Trial registration

Publications

Efficacy and safety of apatinib for the treatment of AFP-producing gastric cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets