Treatment Rationale and Design for APPLE (WJOG11218L): A Multicenter, Open-Label, Randomized Phase 3 Study of Atezolizumab and Platinum/Pemetrexed With or Without Bevacizumab for Patients With Advanced Nonsquamous Non-Small-Cell Lung Cancer.

Abstract:

BACKGROUND:First-line treatment of non-small-cell lung cancer (NSCLC) has undergone a paradigm shift to platinum combination therapy together with an immune checkpoint inhibitor (ICI). Bevacizumab is expected to enhance not only chemotherapy but also the efficacy of ICIs through blockade of vascular endothelial growth factor-mediated immunosuppression. We have now designed a randomized phase 3 study (APPLE, WJOG11218L, JapicCTI-194565) to evaluate the additional effect of bevacizumab administered together with platinum combination therapy and the ICI atezolizumab in patients with advanced nonsquamous NSCLC. PATIENTS AND METHODS:Cytotoxic chemotherapy-naive patients aged 20 years or older with a performance status of 0 or 1 are randomly assigned in a 1:1 ratio to receive either atezolizumab plus pemetrexed/carboplatin or atezolizumab, pemetrexed/carboplatin, and bevacizumab. Patients with genetic driver alterations such as those affecting EGFR or ALK are included if they have experienced disease progression or unacceptable adverse effects during treatment with at least one approved tyrosine kinase inhibitor. After 4 cycles of induction therapy, maintenance therapy with atezolizumab plus pemetrexed or with atezolizumab, pemetrexed, and bevacizumab is administered for up to 2 years until evidence of disease progression or development of unacceptable toxicity. The primary end point is progression-free survival. CONCLUSION:This is a phase 3 study to investigate the effect of adding bevacizumab to an ICI and platinum/pemetrexed combination therapy. If the primary objective is achieved, this study will provide a new standard treatment for cytotoxic chemotherapy-naive patients with advanced nonsquamous NSCLC.

journal_name

Clin Lung Cancer

journal_title

Clinical lung cancer

authors

Shiraishi Y,Kishimoto J,Tanaka K,Sugawara S,Daga H,Hirano K,Azuma K,Hataji O,Hayashi H,Tachihara M,Mitsudomi T,Seto T,Nakagawa K,Yamamoto N,Okamoto I

doi

10.1016/j.cllc.2020.03.010

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

472-476

issue

5

eissn

1525-7304

issn

1938-0690

pii

S1525-7304(20)30089-9

journal_volume

21

pub_type

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    pub_type: 杂志文章,随机对照试验

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    更新日期:2009-05-01 00:00:00