A Phase II Clinical Trial of Apatinib in Pretreated Advanced Non-squamous Non–small-cell Lung Cancer

Wu, Fengying; Zhang, Shijia N; Xiong, Anwen; Gao, Guanghui; Li, Wei; Cai, Weiping; Su, Chunxia; Chen, Xiaoxia; Zhou, Fei; Zhao, Jing; Ren, Shengxiang

doi:10.1016/j.cllc.2018.06.002

Cited by 51 publications

(50 citation statements)

References 28 publications

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“…Most of the treatments are focused on third‐line or higher treatment. Apatinib monotherapy also includes apatinib combined with chemotherapy or targeted drugs . In all clinical studies, monotherapy had poor efficacy.…”

Section: Discussionmentioning

confidence: 99%

Experimental study of the vascular normalization window for tumors treated with apatinib and the efficacy of sequential chemotherapy with apatinib in lung cancer‐bearing mice and patients

Liu

Wang

et al. 2020

Cancer Medicine

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In the tumor vascular system, the vascular structure is disordered, the morphology is abnormal, and the structure of the blood vessel walls is incomplete, leading to leakage of the blood vessel wall, elevated interstitial fluid pressure, and elevated blood flow resistance. These alterations lead to local microenvironmental changes, which mainly manifest as a lack of oxygen and acidosis, further affecting the efficacy of chemotherapy drugs. Antiangiogenic drugs can normalize the abnormalities caused by tumor angiogenesis, thereby transferring oxygen and drugs to tumor cells more efficiently through normalized blood vessels and enhancing the efficacy of chemotherapy drugs. Apatinib is a specific VEGFR-2 inhibitor that blocks the transmission of the VEGF/VEGFR-2 signaling pathway. In this study, we constructed a nude mouse xenograft model of lung cancer and administered apatinib at different doses and times to detect the normalization of reactive blood vessels through VEGF, α-SMA, college-IV, HIF-1α, and MMP. The ultrastructure of tumor blood vessels was observed by electron microscopy, and the dose and timing of apatinib-induced normalization of lung cancer in nude mice were confirmed. Then, we observed the inhibitory effect of apatinib combined with pemetrexed on transplanted tumors of lung cancer cells in nude mice at different time points and observed whether combination pemetrexed chemotherapy showed more significant effects in the time window of vascular normalization induced by apatinib. The inhibition of the growth of transplanted tumors was examined. Then 20 patients with advanced non-small cell lung cancer were enrolled, and apatinib sequential chemotherapy drugs were applied as a third-line chemotherapy regimen to observe its clinical efficacy.

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Section: Discussionmentioning

confidence: 99%

Experimental study of the vascular normalization window for tumors treated with apatinib and the efficacy of sequential chemotherapy with apatinib in lung cancer‐bearing mice and patients

Liu

Wang

et al. 2020

Cancer Medicine

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“…30 The efficacy and safety of apatinib were further confirmed in advanced or metastatic gastric cancer, breast cancer, ovarian cancer, lung cancer, and liver cancer by recent clinical trials. 13,14,[18][19][20][21][22] These data suggest that apatinib was a favorable choice as rescue therapy for the advanced patients with ≥2 lines of chemotherapy failure. Nevertheless, the therapeutic value of apatinib in cervical cancer is still unknown.…”

Section: Discussionmentioning

confidence: 94%

“…14 Several papers indicated that apatinib was an appropriate choice for chemo-refractory malignancies. [15][16][17] Although some papers have demonstrated that apatinib was effective and safe for advanced or metastatic gastric cancer, breast cancer, ovarian cancer, lung cancer, and liver cancer, 13,14,[18][19][20][21][22] doubts still exist about whether it is an appropriate choice for patients with advanced cervical cancer. Therefore, the aim of this retrospective study was to assess the efficacy and safety of apatinib in advanced cervical cancer patients with ≥2 lines of chemotherapy failure.…”

Section: Introductionmentioning

confidence: 99%

Clinical Value Of Apatinib As A Salvage Treatment In Patients With Chemo-Refractory Advanced Cervical Cancer

Su¹,

Gao²,

Ye³

et al. 2019

OTT

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Patients had to have failed at least 2 lines of chemotherapy prior to receiving apatinib. The clinical tumor response was evaluated after 4 weeks of apatinib treatment, and then every 8 weeks (two cycles). Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and adverse events were evaluated. Results: Twenty-five patients were included in this study. The median PFS was 5.8 months (95% CI, 4.65-6.95), and the median OS was 12.2 months (95% CI, 8.99-15.41). ORR was 48% and DCR was 96%. Complete response was not observed. The most common adverse events in this study (all grades) were hand-foot syndrome (48%), hypertension (20%), and mouth mucositis (20%). Conclusion: Apatinib monotherapy showed good therapeutic value with tolerable adverse events for patients with chemo-refractory advanced cervical cancer.

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“…27,28 Interestingly, the mOS in our study was 10.05 months, which was slightly longer than that reported in other research studies of apatinib mesylate. 29,30 We speculate that this effect may be attributed to the continued approval of immunotherapy drugs and anlotinib in China in 2018 Consequently, patients with NSCLC had the opportunity to receive immunotherapy and other targeted drugs in subsequentline treatment, which had been shown to be effective and offered survival benefit to the patients. 31 Furthermore, the results of the polymorphism analysis in our study were partly consistent with those of a previous study conducted by Scartozzi et al 32 A total of 148 patients with advanced hepatocellular cancer who received sorafenib were included in the ALICE-1 study.…”

Section: Dovepressmentioning

confidence: 99%

Clinical Outcomes and Safety of Apatinib Mesylate in the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer in Patients Who Progressed After Standard Therapy and Analysis of the KDR Gene Polymorphism

Song

Zhao

Zuo

et al. 2020

OTT

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Purpose: This study investigated the clinical outcomes and safety of apatinib mesylate in the treatment of advanced non-squamous non-small cell lung cancer (NSCLC) in patients who progressed after standard therapy, and analyzed the kinase insert domain receptor (KDR) gene polymorphism. Methods: A total of 135 patients with advanced non-squamous NSCLC who received apatinib mesylate were included. Objective response rates were evaluated. Subsequently, progression-free survival (PFS) and overall survival (OS) were assessed and safety data were recorded. Additionally, peripheral blood and biopsy cancer tissue specimens were collected from the patients with NSCLC for the genotyping of the genetic polymorphism and mRNA expression of the KDR gene, respectively. Analysis on the association between genotypes and prognosis was conducted. Results: The objective response rate of the 135 patients with NSCLC was 18.52%, disease control rate was 65.19%, median PFS was 3.95 months, and median OS was 10.05 months. Regarding the KDR gene polymorphism analysis, the distribution of the 4397T>C polymorphism genotypes was in accordance with the Hardy-Weinberg Equilibrium (P=0.868). Moreover, the prognosis analysis indicated that the median PFS of patients with the CC/TC and TT genotypes was 2.80 and 4.80 months, respectively (P=0.002). Furthermore, the median OS of patients with the two genotypes was 9.10 and 10.56 months, respectively (P=0.041). The multivariate Cox regression analysis showed that the TC/CC genotypes were an independent factor for PFS (odds ratio: 1.72, P=0.009). There was no correlation between the polymorphism and adverse reactions. Additionally, the mRNA expression analysis suggested that the mRNA levels of KDR in cancer tissues were significantly different between the TT and TC/CC genotypes (P<0.001). Conclusion: The clinical outcomes of treatment with apatinib mesylate for advanced nonsquamous NSCLC in patients who progressed after standard therapy may be influenced by the KDR 4397T>C polymorphism through mediation of the mRNA expression of KDR.

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A Phase II Clinical Trial of Apatinib in Pretreated Advanced Non-squamous Non–small-cell Lung Cancer

Cited by 51 publications

References 28 publications

Experimental study of the vascular normalization window for tumors treated with apatinib and the efficacy of sequential chemotherapy with apatinib in lung cancer‐bearing mice and patients

Experimental study of the vascular normalization window for tumors treated with apatinib and the efficacy of sequential chemotherapy with apatinib in lung cancer‐bearing mice and patients

<p>Clinical Value Of Apatinib As A Salvage Treatment In Patients With Chemo-Refractory Advanced Cervical Cancer</p>

<p>Clinical Outcomes and Safety of Apatinib Mesylate in the Treatment of Advanced Non-Squamous Non-Small Cell Lung Cancer in Patients Who Progressed After Standard Therapy and Analysis of the <em>KDR</em> Gene Polymorphism</p>

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