《柳叶刀》(The Lancet)近期发表两项卵巢癌相关随机对照试验。ENGOT-ov65/KEYNOTE-B96试验提示,在既往接受过1-2线全身治疗的铂耐药复发性卵巢癌患者中,帕博利珠单抗联合每周紫杉醇(联合或不联合贝伐珠单抗)可显著改善无进展生存期和总生存期,支持将该方案作为这类人群的一种新的治疗选择。ROSELLA试验提示,在铂耐药卵巢癌患者中,白蛋白结合型紫杉醇加用瑞拉可兰可显著延长总生存期,且无需进行生物标志物筛选。研究结果支持将瑞拉可兰联合白蛋白结合型紫杉醇作为铂耐药卵巢癌患者的一种潜在新标准治疗方案。识别文中二维码或点击文末阅读原文,查阅原文。



图片


帕博利珠单抗联合每周紫杉醇治疗铂耐药复发性卵巢癌(ENGOT-ov65/KEYNOTE-B96):一项多中心、随机、双盲、3期试验


背景


上皮性卵巢癌易复发并对铂类化疗产生耐药性。本研究旨在探讨,在既往接受过1-2线全身治疗的铂耐药复发性卵巢癌患者中,在每周紫杉醇(联合或不联合贝伐珠单抗)基础上加用帕博利珠单抗,相比每周紫杉醇(联合或不联合贝伐珠单抗),能否改善无进展生存期和总生存期。


方法


ENGOT-ov65/KEYNOTE-B96是一项随机、双盲、3期试验,在美洲、亚洲、欧洲和大洋洲25个国家的187个妇科肿瘤中心开展。试验纳入标准为:年龄≥18岁,经组织学确诊为上皮性卵巢癌、输卵管癌或原发性腹膜癌,既往接受过1-2线全身治疗(包括至少一种含铂方案),且在末次铂类治疗后6个月内出现进展。参与者按1:1比例随机分配接受:静脉注射帕博利珠单抗400mg(每6周1次,最多持续18个周期)联合开放标签的静脉注射紫杉醇(每21天周期的第1、8、15天给药80mg/m²),或静脉注射安慰剂(生理盐水,每6周1次,最多持续18个周期)联合开放标签的静脉注射紫杉醇(每21天周期的第1、8、15天给药80mg/m²)。研究者可酌情使用贝伐珠单抗(静脉注射,10mg/kg,每2周1次)。分层随机化按照是否计划使用贝伐珠单抗、地区及PD-L1综合阳性评分(CPS)进行。主要终点为研究者根据实体肿瘤临床疗效评价标准1.1版(RECIST 1.1)评估的无进展生存期;关键次要终点为总生存期。本文将报告两次中期分析及最终分析结果。本研究已在ClinicalTrials.gov官网注册,注册编号为NCT05116189,目前试验已完成。


结果


2021年12月13日至2023年7月3日期间,共有643例女性参与者被随机分配:322例分配至帕博利珠单抗联合紫杉醇组,321例分配至安慰剂联合紫杉醇组。


在第一次中期分析中,与安慰剂联合紫杉醇相比,帕博利珠单抗联合紫杉醇在PD-L1 CPS≥1人群(中位8.3月 vs 7.2月;风险比[HR]: 0.72;95% CI: 0.58-0.89;p=0.0014;α=0.012)及总人群(中位8.3月 vs 6.4月;HR: 0.70;95% CI: 0.58-0.84;p<0.0001;α=0.0023)中均显著改善无进展生存期,达到预设的确证性疗效标准。在第二次中期分析中,PD-L1 CPS≥1人群的总生存期显著改善(中位18.2月 vs 14.0月;HR: 0.76;95% CI: 0.61-0.94;p=0.0053;α=0.0083)。在最终分析中,总人群的总生存期显著改善(中位17.7月 vs 14.0月;HR: 0.82;95% CI: 0.69-0.97;p=0.011;α=0.024)。


在帕博利珠单抗联合紫杉醇组中,320例参与者中的217例(68%)发生≥3级治疗相关不良事件,而安慰剂联合紫杉醇组为318例中的176例(55%)。最常见的治疗相关不良事件(任意级别)包括贫血、周围神经病变、脱发、乏力和恶心。帕博利珠单抗联合紫杉醇组有4例参与者(1%)因治疗相关不良事件死亡(结肠炎、间质性肺病、急性髓系白血病和肠穿孔),安慰剂联合紫杉醇组则有5例参与者(2%)因治疗相关不良事件死亡(心力衰竭、肠穿孔[2例]和大肠穿孔[2例])。


图片

Progression-free survival


图片

Overall survival


解释


在既往接受过1-2线全身治疗的铂耐药复发性卵巢癌患者中,帕博利珠单抗联合每周紫杉醇(联合或不联合贝伐珠单抗)可显著改善无进展生存期和总生存期,支持将该方案作为这类人群的一种新的治疗选择。

Funding

Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA.

Declaration of interests

NC reports grants or contracts from AstraZeneca and GSK (paid to institution), payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, MSD, GSK, Eisai, AbbVie, Pharma&, and Corcept; support for attending meetings or travel from GSK, AstraZeneca, and AbbVie; participation on a Data Safety Monitoring Board or Advisory Board from Roche, AstraZeneca, MSD, GSK, Immunogen, Eisai, Oncxerna, Nuvation Bio, Gilead, Regeneron, Novocure, Seagen, AbbVie, Lilly, BeOne, and Biontech; medical writing assistance from MSD; and participation in the Scientific Committee ACTO and the Member Nomination Committee ESMO (unpaid). EZ reports grants or contracts from MSD, NCI, DoD, and OCRA; consulting fees from MSD, AbbVie, NextCure, Iovance, 92Biotech, Takeda Oncology, and Apellis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for AstraZeneca; and participation on a Data Safety Monitoring Board or Advisory Board for MSD. ER reports grants or contracts from AstraZeneca, Gilead, MSD, and Roche (paid to institution); and support for attending meetings or travel and participation in a Data Monitoring Committee from Philogen. AS reports Advisory Board and Data Safety Monitoring Board participation, and speaker's honorarium, from GSK, Eisai, and MSD. CG reports consulting fees from GSK, Gilead, MSD, and Adium; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK, MSD, and Adium; and participation on a Data Safety Monitoring Board or Advisory Board from GSK, Gilead, and Adium. KH reports research contracts from Daiichi Sankyo, Eisai, MSD, and Takeda; consulting fees from Chugai, Fuji, and Kyowa Kirin; advisory board fees from Eisai, Takeda, MSD, Regeneron, Roche, Genmab, Sanofi, GSK, and Zymeworks; honoraria from Daiichi Sankyo, AstraZeneca, Chugai, Eisai, Fuji, Genmab, MSD, Takeda, Sanofi, Kyowa Kirin, Kaken, GSK, and Regeneron. MM-M reports research funding from MSD; grants or contracts from Eli Lilly, MSD, and Fortrea (paid to institution); Advisory Board and speaker fees from Eli-Lilly, Roche, Merck GA, MSD, and GSK; and support for attending meetings or travel from Novartis, Merck GA, and Servier. JRK reports grants or contracts from AstraZeneca, Novartis, Philips, Dutch Cancer Society, and Bontius Stichting/LUF (paid to institution); consulting fees from AstraZeneca, Eisai, GSK, Lilly, MSD, Novartis, and Daiichi Sankyo (paid to institution); payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Eisai, GSK, and MSD (paid to institution); support for attending meetings or travel from Daiichi Sankyo (paid to institution); and participation on a Data Safety Monitoring Board or Advisory Board for DSMB, TEIPP, and Alison. ACdM reports grants or contracts, paid to institution, from Amgen, AstraZeneca, Bristol Myers, Squibb, Clovis Oncology, GSK, MSD, Novartis, Regeneron, and Roche; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, Bristol Myers Squibb, GSK, MSD, Novartis, Adium, Daiichi, Pfizer, and AbbVie; support for attending meetings or travel from MSD, Daiichi, and AbbVie; and participation on a Data Safety Monitoring Board or Advisory Board from AstraZeneca, Bristol Myers Squibb, GSK, MSD, Novartis, Roche, and Daiichi. PRD reports consulting fees from MSD, Astellas, and Ipsen; support for attending meetings or travel from Ipsen and MSD; and stock or stock options from Mural Oncology and UCB. J-WK reports a leadership or fiduciary role in the Executive Board of the Asia-Pacific Gynecologic Cancer Trials Group. JS reports research funding from AstraZeneca, Bayer, Clovis Oncology, GSK, Iqvia, Lilly, MSD, Mural, Roche Pharma, and Tesaro (paid to institution); consulting fees from AstraZeneca, Bayer Vital, Bristol Myers, Clovis Oncology, Daiichi Sankyo, Eisai, Encare, Immunogen, Intuitive Surgical, Karyopharm Therapeutics, Merck/Pfizer, MSD, Mundipharma, Novocure, Oncoinvent, PharmaMar, Roche Pharma, Sanofi-Aventis Deutschland, Seagen, and Tubulis; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AMGEN, AstraZeneca, Bayer, Clovis Oncology, Corcept Therapeutics, Daiichi Sankyo, Eisai, Esteve Pharmaceuticals, GSK, Hexal, Incyte Biosciences, Jenapharm, Kyowa Kirin, Medtronic Covidien, Novartis Pharma, Oncoinvent, Pharma&, PharmaMar, Phytolife Nutrition, Roche Pharma, and Vifor Pharma; support for attending meetings or travel from AstraZeneca, GSK, Roche Pharma, Novocure, Immunogen, Incyte, MSD, and Eisai; participation on a Data Safety Monitoring Board or Advisory Board for Immunogen, Incyte, GSK, AstraZeneca, Clovis, Novocure, Bristol Myers Squibb, MSD, Bayer, and PharmaMar; leadership or fiduciary role in European Society of Gynecological Oncology, North-Eastern German Society of Gynecological Oncology, Pan-Arabian Research Society for Gynecological Oncology, Deutsch-Türkische Gynäkologengesellschaft, Deutsche Stiftung Eierstockkrebs, Arbeitsgemeinschaft Gynäkologische Onkologie, and Charité Comprehensive Cancer Center; medical writing assistance from MSD; unpaid participation in editorial boards for International Journal of Gynecological Cancer, Journal of the Turkish-German Gynecological Association, Anticancer Research, Archives of Gyencology and Obstetrics, Research and Treatment, Annals of Gynecology and Obstetrics Research, Journal of Hematology & Multiple Myeloma, and guest editorship for Cancers. M-EP reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK, AstraZeneca, AbbVie, Tecnofarma, Dr Reddy's, and MSD; and support for attending meetings or travel from GSK, AstraZeneca, Roche, AbbVie, and MSD. SH reports participation on a Data Safety Monitoring Board or Advisory Board and advisory or consulting fees from AstraZeneca, Eisai, MSD, GSK, and AbbVie. CZ reports honoraria for participation in the Delphi study from Daiichi Sankyo and AstraZeneca; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Roche, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, MSD, Eisai, GSK, Menarini Stemline, Exact Sciences, and Gilead; support for attending meetings or travel from Roche, Novartis, Pfizer, AstraZeneca, Daiichi Sankyo, MSD, Eisai, GSK, and Gilead; and participation on a Data Safety Monitoring Board or Advisory Board for Roche, Novartis, Pfizer, Lilly, AstraZeneca, Daiichi Sankyo, MSD, Eisai, GSK, Menarini Stemline, Exact Sciences, and Gilead. BJM reports consulting fees from AstraZeneca, BioNtech, Corcept, DSI, Eisai, Eli Lilly, Genmab/Seagen/Pfizer, GOG Foundation, GSK, Immunogen/Abbvie, Incyte, Karyopharm, MSD, Mersana, Mural/Alkermes, Myriad, Natera, Novartis, Novocure, OncoC4, Panavance, Pharma&, ProfoundBio/Genmab, Regeneron, Roche/Genentech, Sutro, Tubulis, Verastem, Zentalis, and Zymeworks; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, DSI, Eisai, GSK, Immunogen/AbbVie, and MSD. RLC reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, MSD, GSK, Karyopharm, Faeth, Genmab, and DSI; participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Genmab/Seagen, GSK, Immunogen, Panavance, Profoundbio, and Roche/Genentech; and leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as a steering committee member for AstraZeneca, GSK, MSD, Roche-Genentech, and Verastem; as a trial chair for Immonogen/AbbVie; as a coordinating principal investigator for Karyopharm; and as a principal investigator for AbbVie, Genmab, Immunogen, MSD, and Roche/Genentech. TDLMR reports grants or contracts from GSK (paid to institution); consulting fees from GSK, AstraZeneca, Eisai, MSD, Pfizer, Novartis, Gilead, AbbVie, Sanofi, and Regeneron; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from GSK, AstraZeneca, MSD, Pfizer, Gilead, and AbbVie; support for attending meetings or travel from Roche, Gilead, and MSD; and participation on a Data Safety Monitoring Board or Advisory Board for MSD. XP, KY, and AMB are employees of Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA, who may own stock or hold stock options in Merck & Co, Rahway, NJ, USA. All other authors declare no competing interests.



DOI: 10.1016/S0140-6736(26)00602-1



图片


瑞拉可兰联合白蛋白结合型紫杉醇治疗铂耐药卵巢癌患者的总生存期(ROSELLA):一项3期随机对照试验


背景


瑞拉可兰是一种选择性糖皮质激素受体拮抗剂,可增加多种类型癌细胞对化疗的敏感性。这项3期ROSELLA试验(GOG-3073、ENGOT-ov72、APGOT-Ov10和LACOG-0223)评估了瑞拉可兰联合白蛋白结合型紫杉醇的疗效和安全性;前期结果显示,与白蛋白结合型紫杉醇单药相比,该联合方案显著改善了铂耐药卵巢癌患者的无进展生存期。本文将报告最终总生存期分析的结果。


方法


在这项开放标签3期试验中,参与者按1:1比例随机分配接受:瑞拉可兰(在白蛋白结合型紫杉醇注射前1天、注射当天及注射后1天口服150mg)联合白蛋白结合型紫杉醇(每28天周期的第1、8、15天静脉注射80mg/m²),或白蛋白结合型紫杉醇单药治疗(按上述方案静脉注射100mg/m²)。试验纳入标准为:年龄≥18岁,既往接受过1-3线抗肿瘤治疗,且为铂耐药(末次铂类治疗后6个月内发生进展)。本试验在澳大利亚、欧洲、拉丁美洲、北美及韩国14个国家的117家医院和社区肿瘤中心开展。双主要终点为:由盲态独立中心评估的无进展生存期及总生存期(自随机分配至任何原因死亡的时间)。其他预设终点包括安全性、第二次无进展生存期(自随机分配至后续抗肿瘤治疗中出现疾病进展或任何原因死亡的时间,以先发生者为准)以及患者报告结局。本试验已在ClinicalTrials.gov官网注册,注册编号为NCT05257408,目前试验仍在进行中。


结果


2023年1月5日至2024年4月8日期间,381例参与者被随机分配至瑞拉可兰联合治疗组(n=188)或白蛋白结合型紫杉醇单药组(n=193)。所有参与者均接受过贝伐珠单抗治疗;167例参与者(44%)既往接受过3线治疗;234例参与者(61%)接受过聚ADP核糖聚合酶抑制剂治疗。在中位随访24.8月时(95% CI: 23.6-25.7),与白蛋白结合型紫杉醇单药相比,瑞拉可兰联合治疗组可在统计学和临床意义上显著改善总生存期(死亡风险比为0.65;95% CI: 0.51-0.83;p=0.0004);两组18个月总生存率分别为46%和27%。与白蛋白结合型紫杉醇单药相比,瑞拉可兰联合治疗组的中位总生存期延长4.1月(16.0月[13.0-18.3] vs 11.9月[10.0-13.8])。两组间后续抗肿瘤治疗情况相似。按研究治疗持续时间校正后,两组的不良事件情况相似。瑞拉可兰联合治疗组最常见的不良事件包括中性粒细胞减少(121例[64%])、贫血(115例[61%])、乏力(101例[54%])和恶心(82例[44%])。与主要分析相比,延长随访未观察到新的安全性信号。

图片


解释


在铂耐药卵巢癌患者中,白蛋白结合型紫杉醇加用瑞拉可兰可显著延长总生存期,且无需进行生物标志物筛选。研究结果支持将瑞拉可兰联合白蛋白结合型紫杉醇作为铂耐药卵巢癌患者的一种潜在新标准治疗方案。END

Funding

Corcept Therapeutics.

Declaration of interests

DL reports grants or contracts from AstraZeneca, AbbVie, GSK, Incyte, MSD, and Corcept; consulting fees from AstraZeneca, AbbVie, GSK, Genmab, MSD, and Pharma&; support for attending meetings or travel from GSK, AbbVie, AstraZeneca, and MSD; and participation on a data safety monitoring board or advisory board at AstraZeneca, AbbVie, Corcept, Genmab, GSK, Regeneron, and MSD. LGl reports support for attending meetings or travel from AbbVie and MSD. DMO reports support for the present manuscript from Corcept; grants or contracts from AbbVie, Advaxis, Agenus, Alkermes, Aravive, Arcus, AstraZeneca, BeiGene, Boston Biomedical, Bristol Myers Squibb, Clovis, Deciphera Pharma, Eisai, EMD Serono, Exelixis, Genentech, Genmab, GSK, the Gynecologic Oncology Group Foundation, F Hoffmann–La Roche, ImmunoGen, Incyte, IOVANCE, Karyopharm, Leap, the Ludwig Institute for Ca, Merck & Co, Merck Sharp & Dohme, Mersana, NCI, Novartis, NovoCure, NRG Oncology, OncoC4, OncoQuest, Pfizer, Precision Therapeutics, Prelude Therapeutics, Regeneron, the RTOG, Rubius Therapeutics, Seattle Genetics, Sutro Biopharma, SWOG, and Verastem; consulting fees from or advisory boards for AbbVie, AstraZeneca, Corcept, Duality Bio, Eli Lilly, GSK, the Gynecologic Oncology Group Foundation, Merck & Co, Merck Sharp & Dohme, Regeneron Pharmaceuticals, Verastem, and Zentalis; and a leadership or fiduciary role at the Gynecologic Oncology Group Foundation Board of Directors. AF reports grants or contracts from AstraZeneca and MSD; consulting fees from Oncoinvent; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Covidien/Medtronic, Pharmaand, and AbbVie; and participation on a data safety monitoring board or advisory board at GSK. LGi reports grants or contracts from Alkermes, Ascendis, AstraZeneca, Bayer, CanariaBio, Corcept Therapeutics, Daiichi Sankyo, Eisai, Espersas, Fortrea, Gilead Science, GOG Foundation, GSK, Immunogen, IMV, K-Group Beta, Karyopharm, Macrogenics, Merck, Mersana Therapeutics, Novocure, OncoQuest Pharmaceuticals, Paraxel International Therapeutics, Pfizer, Pri-Wex Pharma, Roche, Seagen, Shattuck Labs, Sichuan Kelun Biotech, Sutro Bio Pharma, Tesaro, and Verastem; consulting fees from Merck, AbbVie, and GSK; and participation on a data safety monitoring board or advisory board at Merck, GSK, Eisai, and Repare Therapeutics. LM reports medical writing support for this manuscript from Corcept. SQ reports payment or honoraria from AstraZeneca, GSK, MSD, Pharma&, Eisai, and AbbVie; support for attending meetings from GSK, MSD, Pharma&, Eisai, and AbbVie; and participation on a data safety monitoring board or advisory board at AstraZeneca, GSK, MSD, Pharma&, Eisai, and Servier. EH reports participation in advisory board meeting for Corcept. AO reports consulting fees from AbbVie, Agenus, AstraZeneca, Clovis, Corcept, Deciphera, Daiichi Sankyo, Debiopharm International, Eisai, Exelixis, F Hoffmann–La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana, Myriad Genetics, Novocure, OncoXerna, PharmaMar, Regeneron, Sattucklabs, Seagen/Pfizer, Stemline Therapeutics, Sutro Biopharma, TORL Bio Therapeutics, Zentalis, and Zymeworks; payment or honoraria from the NSGO, Peerview, Peervoice, Medscape, Asociación Colombiada de Ginecológos Oncólogos, the ESO, AstraZeneca, and GSK; support for attending meetings from AstraZeneca, PharmaMar, and Roche; and participation on a data safety monitoring board or advisory board for Agenus, AstraZeneca, Clovis Oncology, Corcept, Deciphera Pharmaceuticals, Daiichi Sankyo, Debiopharm International, Eisai, Exelixis, F Hoffmann–La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana, Myriad Genetics, Novocure, OncoXerna, PharmaMar, Regeneron, Sattucklabs, Seagen/Pfizer, Stemline Therapeutics, Sutro Biopharma, TORL Bio Therapeutics, Zentalis, and Zymeworks; and leadership or fiduciary roles at Gynecologic Cancer Intergroup cervical cancer committee chair; ESMO Gyn subject editor guidelines; ESMO Gyn meeting chair; and ESMO Gyn faculty member; and other financial or non-financial interests in Gynecologic Cancer Intergroup, European Society for Medical Oncology, American Society of Clinical Oncology, Spanish Society of Medical Oncology, and the GOG Foundation. MS reports research funding from AstraZeneca, AbbVie, and Gilead; consulting fees from GSK, AbbVie, MSD and AstraZeneca; payment or honoraria from MSD, GSK, AstraZeneca, and AbbVie; support for attending meetings from MSD, AstraZeneca, GSK, and Daiichi Sankyo; and participation on data safety monitoring or advisory boards for MSD, GSK, AstraZeneca, and AbbVie; and leadership or fiduciary role in Sociedade Brasileira de Oncologia Clínica. AC reports support for the present manuscript from Corcept; grants or contracts from Advenchen; payment or honoraria from AbbVie and Pharma&; and support for attending meetings or travel from AbbVie. CP reports stock or stock options in AbbVie, Johnson & Johnson, Pfizer, Amgen, Merck, Gilead, and Bristol Myers Squibb. VS reports payment or honoraria from MSD, AstraZeneca, GSK, Menarini, Pharma&, AbbVie, and Eisai; support for attending meetings or travel from MSD, AstraZeneca, Pharma&, and Menarini; and participation on a data safety monitoring board or advisory board at MSD, AstraZeneca, GSK, Pharma&, AbbVie, and Eisai. BJM reports consulting fees from AstraZeneca, BioNTech, Corcept, DSI, Eisai, Eli Lilly, Genmab–Seagen–Pfizer, the Gynecologic Oncology Group Foundation, GSK, ImmunoGen–AbbVie, Incyte, Karyopharm, Merck, Mersana, Mural/Alkermes, Myriad, Natera, Novartis, Novocore, OncoC4, Panavance, Pharmaand, ProfoundBio, Genmab, Regeneron, Roche–Genentech, Sutro Biopharma, Tubulis, Verastem Oncology, Zentalis, and Zymeworks; and payment or honoraria from AstraZeneca, DSI, Eisai, GSK, Immunogen/AbbVie, and Merck. PF reports consulting fees from AbbVie, GSK, Novartis, and Daiichi; payment or honoraria from MSD, AbbVie, and Novartis; payment for expert testimony from AbbVie, Regeneron, and GSK; support for attending meetings or travel from AbbVie, Novartis, and Daiichi; and participation on data safety monitoring or advisory boards for AbbVie. EM reports grants or contracts from Stanford Cancer Institute. BS reports consulting fees from MSD, AstraZeneca, Daiichi Sankyo, Incyte, Seagen, Novocure, Karyopharm, Genmab, Aadi, Regeneron, Immunocore, Gilead, Eisai, Beigene, and GSK. EG reports participation on data safety monitoring or advisory boards for Daiichi Sankyo, Amgen, and MSD; support for attending meetings or travel from MSD; and payment or honoraria from GSK, EISAI, MSD, and AstraZeneca. MCC reports support for attending meetings or travel from AstraZeneca. AD reports support for attending meetings or travel from GSK, Novartis, AstraZeneca, and Gilead. CC reports consulting fees, payment or honoraria, and participation on data safety monitoring or advisory boards for AstraZeneca and GSK; and leadership or fiduciary role at Abracadabra advocacy group. GA reports payment or honoraria from GSK, AstraZeneca, and Pharmaand; and support for attending meetings or travel from GSK and AstraZeneca. TVG reports grants or contracts from Amgen, AstraZeneca, and Roche; consulting fees from AbbVie, AstraZeneca, BeiGene, BioNTech, Cancer Communications and Consultancy, Daiichi Sankyo, Eisai, Eli Lilly, Genmab, GSK, ImmunoGen, Incyte, Karyopharm, MSD–Merck, OncXerna, Seagen, TORL Bio Therapeutics, Tubulis, Verastem, and Zentalis; honoraria for lectures from AbbVie, AstraZeneca, Eisai, GSK, ImmunoGen, and MSD; support for attending meetings from ImmunoGen, MSD, and PharmaMar; and leadership or fiduciary role as the Chair of the Belgian and Luxembourg Gynaecological Oncology Group. AS reports consulting fees from MSD, AstraZeneca, and AbbVie; payments or honoraria from MSD and AstraZeneca; support for attending meetings from AstraZeneca and MSD; and participation on a data safety monitoring board or advisory board at AstraZeneca, MSD, and AbbVie. LKD reports support for the present manuscript and stock or stock options in Corcept. AK-H reports stock or stock options in Corcept and Exelixis. ICT reports support for the present manuscript, employment, and stock or stock options in Corcept; and leadership or fiduciary role as Member of the Board of Directors at Bay Area Biotech-Pharma Statistics Workshop. AMJ reports employment and stock or stock options in Corcept. NC reports support for the present manuscript from Corcept; grants or contracts from AstraZeneca and GSK; payment or honoraria from AstraZeneca, GSK, MSD, AbbVie, Pharmaand, Corcept, and Eisai; support for attending meetings from GSK, AstraZeneca, and AbbVie; participation on data safety monitoring or advisory boards for Roche, AstraZeneca, MSD, Eisai, GSK, ImmunoGen, Oncxerna, Nuvation Bio, Gilead, Regeneron, Novocure, Seagen, AbbVie, Eli Lilly, BeOne, and Biontech; and a leadership role as Chair of the Alleanza Contro il Tumore Ovarico Scientific Committee, and a member of the nomination committee at ESMO. All other authors declare no competing interests.



DOI: 10.1016/S0140-6736(26)00462-9


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