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A phase I dose-reduction study of apatinib combined with pemetrexed and carboplatin in untreated EGFR and ALK negative stage IV non-squamous NSCLC

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Summary

Objective Apatinib is an oral small molecule anti-angiogenic drug. This phase I study aimed to establish the feasible dose of apatinib in combination with pemetrexed plus carboplatin as first-line therapy for epidermal growth factor receptor (EGFR) and anaplasticlymphoma kinase (ALK) negative stage IV non-squamous non-small cell lung cancer (NSCLC). Methods Using a 3 + 3 dose-reduction design, patients received oral apatinib at four dose levels: 750 mg qd, 500 mg qd, 500 mg/day two weeks on/one week off schedule (500 mg schedule 2/1) or 250 mg qd. Pemetrexed (500 mg/m2) plus carboplatin (AUG = 5) was administered every three weeks. Maintenance therapy by apatinib or pemetrexed could be carried on until disease progression or unacceptable toxicity. The feasible dose was determined based on cycle 1 dose-limiting toxicities (DLT); other assessments included safety and antitumor activity according to response evaluation criteria in solid tumors. Result A total of twelve patients were enrolled and cycle 1 DLTs were observed in two patients at 750 mg qd dosage of apatinib (both Grade 3 hypertension), two patients at 500 mg qd (Grade 3 hypertension and Grade 3 hand-foot syndrome), and only one of six patients at 500 mg/day schedule 2/1 (Grade 3 hypertension). The most frequently drug-related adverse events (AEs) were hematological toxicity, hypertension, hand-foot syndrome, and hepatic transaminases elevation. Partial response was observed in four patients of eleven evaluable patients (objective response rate 36.4%), and six patients exhibited stable disease (disease control rate 90.9%). Conclusion In patients with advanced non-squamous NSCLC, the feasible dose of apatinib given with standard-dose pemetrexed and carboplatin was 500 mg/day schedule 2/1. The schedule was generally well tolerated and demonstrated promising clinical benefit in NSCLC.

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Funding

The work was supported by the Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University.

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Authors and Affiliations

  1. Department of Thoracic Oncology, Cancer Center, West China Hospital, Sichuan University, 37 Guoxue Lane, Chengdu, 610041, China

    Meijuan Huang, Youling Gong, Jiang Zhu, Yi Qin, Feng Peng, Li Ren, Zhenyu Ding, Yongmei Liu, Chengzhi Cai, Yongsheng Wang & You Lu

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  1. Meijuan Huang
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Correspondence to You Lu.

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Author Meijuan Huang declares that she has no conflict of interest. Author Youling Gong declares that he has no conflict of interest. Author Jiang Zhu declares that he has no conflict of interest. Author Yi Qin declares that she has no conflict of interest. Author Feng Peng declares that she has no conflict of interest. Author Li Ren declares that she has no conflict of interest. Author Zhenyu Ding declares that he has no conflict of interest. Author Yongmei Liu declares that she has no conflict of interest. Author Chengzhi Cai declares that he has no conflict of interest. Author Yongsheng Wang declares that he has no conflict of interest. Author You Lu declares that he has no conflict of interest.

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This article does not contain any studies with human participants or animals performed by any of the authors. All applicable international, national, and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Huang, M., Gong, Y., Zhu, J. et al. A phase I dose-reduction study of apatinib combined with pemetrexed and carboplatin in untreated EGFR and ALK negative stage IV non-squamous NSCLC. Invest New Drugs 38, 478–484 (2020). https://doi.org/10.1007/s10637-019-00811-6

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