摘要：All authors report medical writing support funded by F Hoffmann-La Roche. L-PA received grants or contracts from AstraZeneca, Bris

小细胞肺癌（SCLC）约占肺癌的15%，大多数患者被诊断时已属广泛期SCLC（ES-SCLC），这类癌症高度致命且难于治疗。《柳叶刀》（The Lancet）发表了自2019年将免疫疗法引入ES-SCLC治疗以来首项3期临床试验的研究结果，结果显示ES-SCLC生存期的显著改善。

针对该疾病，目前推荐的一线治疗为阿替利珠单抗（atezolizumab，一种免疫治疗药物）、加卡铂（carboplatin，一种化疗药物）和依托泊苷（etoposide，一种化疗药物），之后维持免疫治疗。

芦比替定（Lurbinectedin）是一种烷基化剂，通过减缓或阻止癌症细胞生长来发挥作用，已被批准用于治疗化疗期间或化疗后进展的转移性SCLC。在这项3期试验中，研究人员评估了在标准方案中添加芦比替定能否提高一线维持治疗中的无进展生存期和总体生存期。

共653名ES-SCLC患者接受了4个为期21天的诱导治疗周期（阿替利珠单抗、卡铂、依托泊苷）。诱导治疗完成后，没有疾病进展且符合条件的患者（有483名患者）被随机分配接受芦比替定联合阿替利珠单抗的维持治疗，或只接受阿替利珠单抗的维持治疗。

与只使用阿替利珠单抗进行维持治疗的患者相比，使用受芦比替定联合阿替利珠单抗进行维持治疗的患者，死亡或疾病进展的风险降低了46%，死亡风险降低了27%，相当于总生存期增加了2.6个月，无进展生存期增加了3.3个月。使用了芦比替定的患者，其不良事件发生率较高（3或4级不良事件[38% vs 22%]，5级不良事件[5% vs 3%]），这可能是由于芦比替定的治疗暴露时间较长以及药物的骨髓抑制特性。

作者表示，未来的研究需要进一步了解哪些患者将从联合治疗中更多受益，以及关注长期随访的结果。

文章摘要

芦比替定联合阿替利珠单抗一线维持治疗广泛期小细胞肺癌的疗效与安全性（IMforte）：一项随机、多中心、开放标签的3期试验

背景

尽管免疫检查点抑制剂联合铂类化疗的一线方案使广泛期小细胞肺癌（extensive-stage small-cell lung cancer，ES-SCLC）的疗效有所改善，但其生存率仍然很低。本研究旨在比较芦比替定（lurbinectedin）联合阿替利珠单抗（atezolizumab）与仅用阿替利珠单抗作为维持疗法的效果，研究对象为接受了阿替利珠单抗、卡铂和依托泊苷诱导治疗后、未出现进展的ES-SCLC患者。

方法

结果

2021年11月17日至2024年1月11日期间，共筛出895名患者以备入组，其中660人（74%）纳入到诱导阶段。2022年5月24日至2024年4月30日期间，660名患者中有483人（73%）在诱导阶段结束进入到维持治疗阶段，并被随机分配至芦比替定+阿替利珠单抗组（242人）或阿替利珠单抗组（241人）。在随访截止时（2024年7月29日），芦比替定+阿替利珠单抗组经IRF评估的无进展生存期长于阿替利珠单抗组（分层风险比[HR] 0.54[95%CI：0.43-0.67]；p

解释

对于ES-SCLC患者，芦比替定+阿替利珠单抗组的IRF评估的无进展生存期和总生存期均长于阿替利珠单抗组，但不良反应发生率也较高。芦比替定联合阿替利珠单抗为此类患者的一线维持治疗提供了新的治疗选择。END

基金

F Hoffmann-La Roche and Jazz Pharmaceuticals.

竞争利益冲突

All authors report medical writing support funded by F Hoffmann-La Roche. L-PA received grants or contracts from AstraZeneca, Bristol Myers Squibb, Merck Sharpe & Dohme, and Pfizer; reports consulting fees from Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, Mirati, Merck Sharpe & Dohme, Novartis, Pfizer, PharmaMar, Sanofi, Servier, and Takeda; and received honoraria from AstraZeneca, Janssen, Merck, and Mirati; and the laboratory and clinical research facility where he conducts research was funded by Fundación Cris, Instituto de Salud Carlos III (INGENIO-PMP21/00107, PMPTA22/00167, PI20/00870, AC20/0070), the Madrid Regional Government (iLung-P2022/BMD-7437), and the Asociación Española Contra el cancer (AECC; RETOS245794PAZA). HB received grants or contracts (to their institution) from Amgen, Bristol Myers Squibb, and Eli Lilly; received consulting or advisory fees from AbbVie, Amgen, AstraZeneca, Axiom, Bayer, BeiGene, BerGenBio, BioNTech, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, EMD-Serono, Guardant, Genentech, Genmab, Gilead, Grid Therapeutics, Iobiotech, iTEO, Janssen, Jazz Pharmaceuticals, Merck, Mirati, Natera, Novartis, Novocure, Oncocyte, Pfizer, PharmaMar, Puma, RAPT, Regeneron, Takeda, and Summit; received honoraria from Amgen, Daiichi Sankyo, Janssen, Jazz Pharmaceuticals, Pfizer, and Regeneron; received support for attending meetings and/or travel from Amgen, Bristol Myers Squibb, Eli Lilly, EMD-Serono, Genentech, Jazz Pharmaceuticals, Merck, Mirati, and Regeneron; participated in a data safety monitoring board or advisory board for Incyte, Novartis, Takeda, University of Pennsylvania CAR T Program, and Springworks; held stock options from Inspirna, Nucleai, and Sonnetbio; and received medical writing services funded by Amgen, AstraZeneca, Bristol Myers Squibb, F Hoffmann-La Roche, Jazz Pharmaceuticals, Merck, and Mirati. SVL received grants or contracts (to their institution) from AbbVie, Alkermes, AstraZeneca, Bristol Myers Squibb, Cogent Biosciences, Duality, Elevation Oncology, Ellipses, Genentech, Gilead, Merck, Merus, Nuvalent, OSE Immunotherapeutics, Puma, RAPT, Synthekine, and SystImmune; and consulting fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Genentech/F Hoffmann-La Roche, Gilead, GlaxoSmithKline, Guardant Health, Johnson & Johnson, Jazz Pharmaceuticals, Merck, Merus, Mirati, Natera, Novartis, OSE Immunotherapeutics, Pfizer, RAPT, Regeneron, Revolution Medicines, Takeda, and Yuhan. SP received grants or contracts (to their institution) from Amgen, Arcus, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche/Genentech, GlaxoSmithKline, iTeos, Mirati, MSD, PharmaMar, Pfizer, Promontory Therapeutics, and Seattle Genetics; received consulting fees from AbbVie, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, BerGenBio, Bicycle Therapeutics, Biocartis, BioInvent, BioNTech, Blueprint Medicines, Bristol Myers Squibb, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F Hoffmann-La Roche/Genentech, Foundation Medicine, F-Star, Genmab, Genzyme, Gilead, GlaxoSmithKline, Hutchmed, Illumina, Incyte, Ipsen, iTeos, Janssen, Merck Serono, Merrimack, Mirati, MSD, Novartis, Novocure, Nuvation Bio, Nykode Therapeutics, Pfizer, Pharma Mar, Promontory Therapeutics, Qlucore, Regeneron, Sanofi, Seattle Genetics, Takeda, and Zymeworks; payment or honoraria (to their institution) from AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Foundation Medicine, GlaxoSmithKline, Illumina, Ipsen, Merck Sharpe & Dohme, Mirati, Novartis, Pfizer, Sanofi, Seattle Genetics, and Takeda; received support for attending meetings and/or travel (to their institution) from AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F Hoffmann-La Roche/Genentech, Merck Sharpe & Dohme, Novartis, Pfizer, and Takeda; and participated in a data safety monitoring board or advisory board for AbbVie, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, BerGenBio, Bicycle Therapeutics, Biocartis, BioInvent, BioNTech, Blueprint Medicines, Bristol Myers Squibb, Boehringer Ingelheim, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F Hoffmann-La Roche/Genentech, Foundation Medicine, F-Star, Genmab, Genzyme, Gilead, GlaxoSmithKline, Hutchmed, Illumina, Incyte, Ipsen, iTeos, Janssen, Merck Serono, Merrimack, Mirati, MSD, Novartis, Novocure, Nuvation Bio, Nykode Therapeutics, PharmaMar, Promontory Therapeutics, Pfizer, Qlucore, Regeneron, Sanofi, Seattle Genetics, Takeda, and Zymeworks. RSH received consulting fees from Amgen, ArriVent, AstraZeneca, Bristol Myers Squibb, Candel Therapeutics, Catalym, Checkpoint Therapeutics, Cybrexa Therapeutics, Eli Lilly, EMD Serono, F Hoffmann-La Roche, Genentech, Gilead, I-Mab Biopharma, Immunocore, Janssen, Mediflix, Merck, NextCure, Novartis, Pfizer, Regeneron, and Sanofi; received support for attending meetings and/or travel from American Association for Cancer Research, International Association for the Study of Lung Cancer, Society for Immunotherapy of Cancer, Southwest Oncology Group, and Friends of Cancer Research; participated in a data safety monitoring board or advisory board for AstraZeneca, Candel Therapeutics, Checkpoint Therapeutics, Cybrexa Therapeutics, I-Mab Biopharma, Immune-Onc Therapeutics, Immunocore, and Novartis; held leadership roles for American Association for Cancer Research, International Association for the Study of Lung Cancer, Society for Immunotherapy of Cancer, Southwest Oncology Group, and Friends of Cancer Research; held stock or stock options in Bolt Biotherapeutics, Checkpoint Therapeutics, and Immunocore Holdings; and was a non-executive board member for Immunocore Holdings and Junshi Pharmaceuticals. KS received payment or honoraria from AstraZeneca, Bristol Myers Squibb, F Hoffmann-La Roche, Janssen, Medison, Merck, Merck Sharpe & Dohme, Pfizer, and Takeda; support for attending meetings and/or travel from AstraZeneca, Merck Sharpe & Dohme, and Takeda; and participated in a data safety monitoring board or advisory board for BeiGene and Medison. MM received payment or honoraria from Amgen, AstraZeneca, Beigene, Boehringer Ingelheim, F Hoffmann-La Roche, Johnson & Johnson, Helssin, Immedica, Merck Sharpe & Dohme, Pfizer, and Takeda; support for attending meetings and/or travel from AstraZeneca, F Hoffmann-La Roche, and Merck Sharpe & Dohme; and participated in a data safety monitoring board or advisory board for Bayer. MANS received consulting fees from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, Gilead, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, and Takeda; received payment or honoraria from Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, F Hoffmann-La Roche, Gilead, Janssen, Merck Sharpe & Dohme, Novartis, Pfizer, and Takeda; and received support for attending meetings and/or travel from Bayer, Bristol Myers Squibb, F Hoffmann-La Roche, Merck Sharpe & Dohme, Novartis, and Pfizer. GC received payment or honoraria from Amgen, AstraZeneca, F Hoffmann-La Roche, Merck Sharpe & Dohme, Pfizer, and Takeda; received support for attending meetings and/or travel from Merck Sharpe & Dohme, Pfizer, and Takeda; and participated in a data safety monitoring board or advisory board for AstraZeneca and Bristol Myers Squibb. RBC received an investigational grant from F Hoffmann-La Roche; received payment or honoraria from Amgen, AstraZeneca, Bristol Myers Squibb, F Hoffmann-La Roche, Merck Sharpe & Dohme, Pfizer, and Takeda; and participated in a data safety monitoring board or advisory board for AstraZeneca, Bristol Myers Squibb, F Hoffmann-La Roche, and Takeda. KHL received research funding from Merck; and received consulting fees from Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Johnson & Johnson/Janssen, Merck, Merck Sharpe & Dohme, Pfizer, Takeda, and Yuhan. MLJ received grants or contracts (to their institution) from AbbVie, Adaptimmune, Amgen, Arcus, Array BioPharma, ArriVent, Artios, AstraZeneca, Bayer, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, City of Hope National Medical Center, Conjupro Biotherapeutics, Corvus Pharmaceuticals, Curis, CytomX, Daiichi Sankyo, Dracen Pharmaceuticals, Eli Lilly, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, F Hoffmann-La Roche/Genentech, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Harpoon, Helsinn Healthcare, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immuneering Corporation, Immunitas Therapeutics, Immunocore, Impact Therapeutics, Incyte, Janssen, Kartos Therapeutics, LockBody Therapeutics, Loxo Oncology, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, NextPoint Therapeutics, Novartis, Numab Therapeutics, Nuvalent, OncoC4, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Theraeputics, Sanofi, Seven and Eight Biopharmaceuticals/Birdie Pharmaceuticals, Shattuck Labs, Silicon Therapeutics, Summit Therapeutics, Syndax Pharmaceuticals, Systimmune, Taiho Oncology, Takeda, TCR2 Therapeutics, Tempest Therapeutics, TheRas, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, Vividion, Vyriad, and Y-mAbs Therapeutics; and received consulting fees from AbbVie, Alentis Therapeutics, Amgen, Arcus Biosciences, AstraZeneca, Biohaven Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, D3 Bio, Daiichi Sankyo, Eli Lilly, Fate Therapeutics, F Hoffmann-La Roche/Genentech, Gilead, GlaxoSmithKline, Gritstone Oncology, Hookipa Biotech, Immunocore, Janssen, Jazz Pharmaceuticals, Merck, Mirati Therapeutics, ModeX Therapeutics, Normunity, Novartis, Novocure, Pfizer, Regeneron Pharmaceuticals, Revolution Medicines, Sanofi-Aventis, Seattle Genetics, Synthekine, Takeda, and Zai Laboratory. NK held stock or stock options in F Hoffmann-La Roche. CG received payment or honoraria from AstraZeneca, Boehringer Ingelheim, Daiichi Sankyo, F Hoffmann-La Roche, Merck Sharpe & Dohme, Novartis, Novocure, PharmaMar, and Takeda. SB received grants or contracts (to self or their institution) from Amgen, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, Eisai, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Novartis, Regeneron, and ZymeWorks; received consulting fees from AstraZeneca, Bristol Myers Squibb, F Hoffmann-La Roche, Janssen, and Merck Sharpe & Dohme; and received support for attending meetings and/or travel from Bristol Myers Squibb, Eli Lilly, Galenica, and Merck Sharpe & Dohme. JSA received payment or honoraria from Amgen Korea, AstraZeneca Korea, Bayer Korea, BC World, Boehringer Ingelheim, Boryung, Daiichi Sankyo Korea, Eli Lilly Korea, F Hoffmann-La Roche Korea, Kyowa Kirin, LG Chem, Menarini Korea, Nokwon Medical, Novartis Korea, Pfizer, Samyang, Takeda, and Yuhan; and participated in a data safety monitoring board or advisory board for Daiichi Sankyo Korea, F Hoffmann-La Roche, Guardant, Immuneoncia, Pfizer, Pharmbio, Therapex Korea, and Yuhan. RC received grants or contracts (to institution) from AstraZeneca, ArriVent, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, OSE Immunotherapeutics, PharmaMar, and Taiho; received consulting fees from ArriVent, AstraZeneca, BioNTech, Bristol Myers Squibb, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck Sharpe & Dohme, Pfizer, PharmaMar, and Takeda; received payment or honoraria from AstraZeneca, BeiGene, GlaxoSmithKline, Janssen, Regeneron, and Takeda; received support for attending meetings and/or travel from Janssen and Takeda; participated in a data safety monitoring board or advisory board for ArriVent, AstraZeneca, Janssen, and PharmaMar; held a leadership or fiduciary role in the European Society for Medical Oncology Educational Publication Working Group and The European Organisation for Research and Treatment of Cancer Lung Group; and held stock or stock options in Supportive Care UK and Leaders in Oncology Care at the Christie Private Care. T-YY received payment or honoraria from AstraZeneca, Daiichi Sankyo, F Hoffmann-La Roche, Janssen, Merck Sharpe & Dohme, and Pfizer; and received support for attending meetings and/or travel from AstraZeneca, Daiichi Sankyo, F Hoffmann-La Roche, Janssen, Merck Sharpe & Dohme, and Pfizer. YK received consulting fees from F Hoffmann-La Roche, Novartis, and Pfizer; received payment or honoraria from AstraZeneca, Daiichi Sankyo, F Hoffmann-La Roche, Merck Sharpe & Dohme, Novartis, and Pfizer; and received support for attending meetings and/or travel from Amgen, AstraZeneca, F Hoffmann-La Roche, Gilead, and Novartis. MB, VC, VG, and Y-CL are employed by F Hoffmann-La Roche; hold stock or stock options in F Hoffmann-La Roche; and received support for attending meetings and/or travel from F Hoffmann-La Roche. DC is employed by Jazz Pharmaceuticals; holds stock or stock options in Jazz Pharmaceuticals; and received support for attending meetings and/or travel from Jazz Pharmaceuticals. KB, GC, and RI are employed by Jazz Pharmaceuticals; and hold stock or stock options in Jazz Pharmaceuticals. MR received consulting fees from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, Mirati, Merck Sharpe & Dohme, Novartis, Pfizer, Regeneron, and Sanofi; received payment or honoraria from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, Mirati, Merck Sharpe & Dohme, Novartis, Pfizer, Regeneron, and Sanofi; received support for attending meetings and/or travel from Amgen, AstraZeneca, BeiGene, Bristol Myers Squibb, Boehringer-Ingelheim, Daiichi Sankyo, Eli Lilly, F Hoffmann-La Roche, GlaxoSmithKline, Janssen, Merck, Mirati, Merck Sharpe & Dohme, Novartis, Pfizer, Regeneron, and Sanofi; and participated in a data safety monitoring board or advisory board for Daiichi Sankyo and Sanofi. TC declares no competing interests.

文章翻译仅供参考，所有内容以论文原文为准。

https://doi.org/10.1016/S0140-6736(25)01011-6

来源：柳叶刀TheLancet