Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma.

IF 96.2 1区医学 Q1 MEDICINE, GENERAL & INTERNAL New England Journal of Medicine Pub Date : 2024-11-07 Epub Date: 2024-06-02 DOI:10.1056/NEJMoa2402604

Christian U Blank, Minke W Lucas, Richard A Scolyer, Bart A van de Wiel, Alexander M Menzies, Marta Lopez-Yurda, Lotte L Hoeijmakers, Robyn P M Saw, Judith M Lijnsvelt, Nigel G Maher, Saskia M Pulleman, Maria Gonzalez, Alejandro Torres Acosta, Winan J van Houdt, Serigne N Lo, Anke M J Kuijpers, Andrew Spillane, W Martin C Klop, Thomas E Pennington, Charlotte L Zuur, Kerwin F Shannon, Beatrijs A Seinstra, Robert V Rawson, John B A G Haanen, Sydney Ch'ng, Kishan A T Naipal, Jonathan Stretch, Johannes V van Thienen, Michael A Rtshiladze, Sofie Wilgenhof, Rony Kapoor, Aafke Meerveld-Eggink, Lindsay G Grijpink-Ongering, Alexander C J van Akkooi, Irene L M Reijers, David E Gyorki, Dirk J Grünhagen, Frank M Speetjens, Sonja B Vliek, Joanna Placzke, Lavinia Spain, Robert C Stassen, Mona Amini-Adle, Céleste Lebbé, Mark B Faries, Caroline Robert, Paolo A Ascierto, Rozemarijn van Rijn, Franchette W P J van den Berkmortel, Djura Piersma, Andre van der Westhuizen, Gerard Vreugdenhil, Maureen J B Aarts, Marion A M Stevense-den Boer, Victoria Atkinson, Muhammad Khattak, Miles C Andrews, Alfons J M van den Eertwegh, Marye J Boers-Sonderen, Geke A P Hospers, Matteo S Carlino, Jan-Willem B de Groot, Ellen Kapiteijn, Karijn P M Suijkerbuijk, Piotr Rutkowski, Shahneen Sandhu, Astrid A M van der Veldt, Georgina V Long

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引用次数: 0

Abstract

Background: In phase 1-2 trials in patients with resectable, macroscopic stage III melanoma, neoadjuvant immunotherapy was more efficacious than adjuvant immunotherapy.

Methods: In this phase 3 trial, we randomly assigned patients with resectable, macroscopic stage III melanoma to two cycles of neoadjuvant ipilimumab plus nivolumab followed by surgery or surgery followed by 12 cycles of adjuvant nivolumab. Only patients in the neoadjuvant group with a partial response or nonresponse received adjuvant treatment. The primary end point was event-free survival.

Results: A total of 423 patients underwent randomization. At a median follow-up of 9.9 months, the estimated 12-month event-free survival was 83.7% (99.9% confidence interval [CI], 73.8 to 94.8) in the neoadjuvant group and 57.2% (99.9% CI, 45.1 to 72.7) in the adjuvant group. The difference in restricted mean survival time was 8.00 months (99.9% CI, 4.94 to 11.05; P<0.001; hazard ratio for progression, recurrence, or death, 0.32; 99.9% CI, 0.15 to 0.66). In the neoadjuvant group, 59.0% of patients had a major pathological response, 8.0% had a partial response, 26.4% had a nonresponse (>50% residual viable tumor), and 2.4% had progression; in 4.2%, surgery had not yet been performed or was omitted. The estimated 12-month recurrence-free survival was 95.1% in patients in the neoadjuvant group who had a major pathological response, 76.1% among those with a partial response, and 57.0% among those with a nonresponse. Adverse events of grade 3 or higher that were related to systemic treatment occurred in 29.7% of patients in the neoadjuvant group and in 14.7% in the adjuvant group.

Conclusions: Among patients with resectable, macroscopic stage III melanoma, neoadjuvant ipilimumab plus nivolumab followed by surgery and response-driven adjuvant therapy resulted in longer event-free survival than surgery followed by adjuvant nivolumab. (Funded by Bristol Myers Squibb and others; NADINA ClinicalTrials.gov number, NCT04949113.).

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新辅助Nivolumab和Ipilimumab治疗可切除的III期黑色素瘤

背景：以可切除的大面积 III 期黑色素瘤患者为对象的 1-2 期试验显示，新辅助免疫疗法比辅助免疫疗法更有效：以可切除的巨大III期黑色素瘤患者为对象的1-2期试验表明，新辅助免疫疗法比辅助免疫疗法更有效：在这项三期试验中，我们按1:1的比例随机分配可切除的大面积III期黑色素瘤患者，让他们接受两个周期的新辅助伊匹单抗加尼伐单抗治疗，然后接受手术治疗，或接受手术治疗，然后接受12个周期的尼伐单抗辅助治疗。只有新辅助组中部分应答或无应答的患者才接受后续辅助治疗。主要终点是无事件生存期：共有423名患者接受了随机分组。中位随访时间为9.9个月，估计新辅助治疗组的12个月无事件生存率为83.7%（置信区间[CI]为99.9%，73.8-94.8），辅助治疗组为57.2%（置信区间[CI]为99.9%，45.1-72.7）。受限平均生存时间的差异为 8.00 个月（99.9% CI，4.94 至 11.05；P50% 残存存活肿瘤），2.4% 的患者病情进展；4.2% 的患者尚未进行手术或放弃手术。在新辅助治疗组中，获得主要病理反应的患者的12个月无复发生存率估计为95.1%，获得部分反应的患者为76.1%，无反应的患者为57.0%。29.7%的新辅助治疗组患者和14.7%的辅助治疗组患者出现了与全身治疗相关的3级或3级以上不良反应：结论：在可切除的大面积III期黑色素瘤患者中，新辅助治疗伊匹单抗加尼伐单抗后再手术和反应驱动辅助治疗的无事件生存期比手术后再辅助治疗尼伐单抗的无事件生存期更长。(由百时美施贵宝等公司资助；NADINA ClinicalTrials.gov 编号：NCT04949113）。

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来源期刊

New England Journal of Medicine 医学-医学：内科

CiteScore

145.40

自引率

0.60%

发文量

1839

审稿时长

1 months

期刊介绍： The New England Journal of Medicine (NEJM) stands as the foremost medical journal and website worldwide. With an impressive history spanning over two centuries, NEJM boasts a consistent publication of superb, peer-reviewed research and engaging clinical content. Our primary objective revolves around delivering high-caliber information and findings at the juncture of biomedical science and clinical practice. We strive to present this knowledge in formats that are not only comprehensible but also hold practical value, effectively influencing healthcare practices and ultimately enhancing patient outcomes.

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