Salvage treatment with apatinib for advanced non-small-cell lung cancer

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Salvage treatment with apatinib for advanced non-small-cell lung cancer

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Author(s): Zhengbo Song ¹ ^, ² , Xinmin Yu ¹ ^, ² , Guangyuan Lou ¹ ^, ² , Xun Shi ¹ ^, ² , Yiping Zhang ¹ ^, ²

Publication date (Electronic): 23 March 2017

Journal: OncoTargets and therapy

Publisher: Dove Medical Press

Keywords: non-small-cell lung cancer, apatinib, VEGF, efficacy

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Abstract

Objective

No definitive chemotherapeutic regimen has been established in patients with non-small-cell lung cancer (NSCLC) who failed second- or third-line treatment. The aim of this study was to evaluate apatinib, a VEGFR-2 inhibitor, in advanced NSCLC as salvage treatment.

Methods

We evaluated the efficacy and toxicity of apatinib in patients with previously treated advanced NSCLC from 2014 to 2015 in Zhejiang Cancer Hospital. Survival analysis was performed by the Kaplan–Meier method.

Results

Forty-two patients were included in the present study. Four patients achieved partial response, and 22 achieved stable disease, representing a response rate of 9.5% and a disease control rate of 61.9%. Median progression-free survival and overall survival were 4.2 and 6.0 months, respectively. The toxicities associated with apatinib were generally acceptable with a total grade 3/4 toxicity of 50%.

Conclusion

Apatinib appears to have some activity against advanced NSCLC when utilized as salvage treatment.

Most cited references 14

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Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil.

Martin Reck, Joachim von Pawel, Petr Zatloukal … (2009)

Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, improves survival when combined with carboplatin/paclitaxel for advanced nonsquamous non-small-cell lung cancer (NSCLC). This randomized phase III trial investigated the efficacy and safety of cisplatin/gemcitabine (CG) plus bevacizumab in this setting. Patients were randomly assigned to receive cisplatin 80 mg/m2 and gemcitabine 1,250 mg/m(2) for up to six cycles plus low-dose bevacizumab (7.5 mg/kg), high-dose bevacizumab (15 mg/kg), or placebo every 3 weeks until disease progression. The trial was not powered to compare the two doses directly. The primary end point was amended from overall survival (OS) to progression-free survival (PFS). Between February 2005 and August 2006, 1,043 patients were randomly assigned (placebo, n = 347; low dose, n = 345; high dose, n = 351). PFS was significantly prolonged; the hazard ratios for PFS were 0.75 (median PFS, 6.7 v 6.1 months for placebo; P = .003) in the low-dose group and 0.82 (median PFS, 6.5 v 6.1 months for placebo; P = .03) in the high-dose group compared with placebo. Objective response rates were 20.1%, 34.1%, and 30.4% for placebo, low-dose bevacizumab, and high-dose bevacizumab plus CG, respectively. Duration of follow-up was not sufficient for OS analysis. Incidence of grade 3 or greater adverse events was similar across arms. Grade > or = 3 pulmonary hemorrhage rates were < or = 1.5% for all arms despite 9% of patients receiving therapeutic anticoagulation. Combining bevacizumab (7.5 or 15 mg/kg) with CG significantly improved PFS and objective response rate. Bevacizumab plus platinum-based chemotherapy offers clinical benefit for bevacizumab-eligible patients with advanced NSCLC.

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Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer.

Xichun Hu, Jian Jian Zhang, Binghe Xu … (2014)

Apatinib is an oral, highly potent tyrosine-kinase inhibitor targeting VEGFR2. Phase I study showed the recommended dose of 750 mg/day with substantial antitumor activity. This phase II study aims to evaluate the optimum dose level for the efficacy and safety of apatinib monotherapy in heavily pretreated patients with metastatic triple negative breast cancer (mTNBC) in China. Phase IIa was first performed among 25 patients previously treated with anthracycline and/or taxane. All patients received apatinib 750 mg/day p.o. in a 4-week cycle. Subsequently, a phase IIb study of 59 patients was activated, with the endpoint progression-free survival (PFS). The dosage of drug for the Phase IIb was determined according to safety, tolerability and efficacy from the phase IIa study. As a result of toxicity associated with the 750 mg dose in phase IIa, the recommended initial dose of apatinib in the phase IIb was 500 mg/day. In phase IIb, grade 3/4 hematologic toxicities were thrombocytopenia (13.6%), leukopenia (6.8%), neutropenia (3.4%) and anemia (1.7%). The most frequent grade 3/4 nonhematologic toxicities were hand-foot syndrome, proteinuria, hypertension, and increased ALT. In the 56 evaluable patients, overall response rate and clinical benefit rate (CBR) were 10.7 and 25.0%, respectively. Median PFS and overall survival were 3.3 (95% CI 1.7-5.0) and 10.6 (95% CI 5.6-15.7) months, respectively. Our results indicate that apatinib dose of 500 mg rather than 750 mg is the recommended starting dose for the heavily pretreated mTNBC patients with measurable rate of partial response and PFS. © 2014 UICC.

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Apatinib: a promising oral antiangiogenic agent in the treatment of multiple solid tumors.

Lori Scott-Sheldon, W A Messersmith, M Jimeno (2015)

Aberrant proangiogenic pathways have long been implicated in tumorigenesis and metastasis. Antiangiogenic therapies have shown efficacy in the treatment of a variety of solid tumors including lung, breast, colon, glioblastomas, and other solid tumor types. Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), is an orally bioavailable agent currently being studied in multiple tumor types. Apatinib has shown a survival benefit in gastric cancer in a phase III trial and non-small cell lung cancer in a phase II trial. With a favorable side effect profile and improved outcomes, apatinib has demonstrated a substantial potential to augment therapeutic options in a variety of tumor types.

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Author and article information

Journal

Journal ID (nlm-ta): Onco Targets Ther

Journal ID (iso-abbrev): Onco Targets Ther

Journal ID (publisher-id): OncoTargets and Therapy

Title: OncoTargets and therapy

Publisher: Dove Medical Press

ISSN (Electronic): 1178-6930

Publication date Collection: 2017

Publication date (Electronic): 23 March 2017

Volume: 10

Pages: 1821-1825

Affiliations

[1 ]Department of Chemotherapy, Zhejiang Cancer Hospital

[2 ]Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Zhejiang province, Hangzhou, People’s Republic of China

Author notes

Correspondence: Yiping Zhang; Xinmin Yu, Department of Chemotherapy, Zhejiang Cancer Hospital, 38 Guangji Road, Hangzhou 310022, People’s Republic of China, Tel +86 571 8812 2182, Fax +86 571 8812 2188, Email zjzlyy16@ 123456163.com ; zjzlyy40@ 123456163.com

Article

Publisher ID: ott-10-1821

DOI: 10.2147/OTT.S113435

PMC ID: 5370069

PubMed ID: 28367065

SO-VID: fd205616-762e-4db9-8181-1c6e77163e39

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The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

OncoTargets and Therapy (submit here)

Salvage treatment with apatinib for advanced non-small-cell lung cancer

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Abstract

Objective

Methods

Results

Conclusion

Most cited references 14

Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil.

Multicenter phase II study of apatinib, a novel VEGFR inhibitor in heavily pretreated patients with metastatic triple-negative breast cancer.

Apatinib: a promising oral antiangiogenic agent in the treatment of multiple solid tumors.

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