小柯机器人

荷兰癌症研究所 C. U. Blank课题组，分析了III期黑色素瘤OpACIN-neo和OpACIN新型辅助免疫疗法的生存期和生物标志物。 这一研究成果于2021年2月8日发表在国际学术期刊《自然-医学》上。

在OpACIN（NCT02437279）1b和OpACIN-neo（NCT02977052）2研究的III期黑色素瘤患者中，辅助性新药ipilimumab加nivolumab表现出较高的病理反应率（pRRs）。虽然结果振奋人心，但缺乏有关这些病理反应持久性以及反应和生存期的基线生物标志物数据。

在随访4年后，OpACIN研究中具有病理反应的患者（n = 7/9患者）不会发生复发。在OpACIN-neo（n = 86）随访者中， 2年内无复发生患者的生存率为84％、达到病理学应答患者的生存率为97％和无应答患者的生存率为36％（P <0.001）。高肿瘤突变负荷（TMB）和高干扰素-γ相关基因表达特征评分（IFN-γ评分）与病理反应和复发风险相关。IFN-γ评分高/TMB高患者的pRR为100％；IFN-γ评分高/TMB低或IFN-γ评分低/TMB高患者的pRR分别为91％和88％；而IFN-γ评分低/ TMB低的患者的pRR只有39％。

这些数据证明了具有病理反应的患者可以长期获益，并显示了TMB和IFN-γ评分在预后预测的潜力。该发现为在III期黑色素瘤中比较新药ipilimumab加nivolumab疗法，与标准辅助疗法加靶向程序性细胞死亡蛋白1（anti-PD-1）的随机3期临床研究提供了强有力的支撑。

附：英文原文

Title: Survival and biomarker analyses from the OpACIN-neo and OpACIN neoadjuvant immunotherapy trials in stage III melanoma

Author: E. A. Rozeman, E. P. Hoefsmit, I. L. M. Reijers, R. P. M. Saw, J. M. Versluis, O. Krijgsman, P. Dimitriadis, K. Sikorska, B. A. van de Wiel, H. Eriksson, M. Gonzalez, A. Torres Acosta, L. G. Grijpink-Ongering, K. Shannon, J. B. A. G. Haanen, J. Stretch, S. Chng, O. E. Nieweg, H. A. Mallo, S. Adriaansz, R. M. Kerkhoven, S. Cornelissen, A. Broeks, W. M. C. Klop, C. L. Zuur, W. J. van Houdt, D. S. Peeper, A. J. Spillane, A. C. J. van Akkooi, R. A. Scolyer, T. N. M. Schumacher, A. M. Menzies, G. V. Long, C. U. Blank

Issue&Volume: 2021-02-08

Abstract: Neoadjuvant ipilimumab plus nivolumab showed high pathologic response rates (pRRs) in patients with macroscopic stage III melanoma in the phase 1b OpACIN (NCT02437279) and phase 2 OpACIN-neo (NCT02977052) studies1,2. While the results are promising, data on the durability of these pathologic responses and baseline biomarkers for response and survival were lacking. After a median follow-up of 4 years, none of the patients with a pathologic response (n=7/9 patients) in the OpACIN study had relapsed. In OpACIN-neo (n=86), the 2-year estimated relapse-free survival was 84% for all patients, 97% for patients achieving a pathologic response and 36% for nonresponders (P<0.001). High tumor mutational burden (TMB) and high interferon-gamma-related gene expression signature score (IFN-γ score) were associated with pathologic response and low risk of relapse; pRR was 100% in patients with high IFN-γ score/high TMB; patients with high IFN-γ score/low TMB or low IFN-γ score/high TMB had pRRs of 91% and 88%; while patients with low IFN-γ score/low TMB had a pRR of only 39%. These data demonstrate long-term benefit in patients with a pathologic response and show the predictive potential of TMB and IFN-γ score. Our findings provide a strong rationale for a randomized phase 3 study comparing neoadjuvant ipilimumab plus nivolumab versus standard adjuvant therapy with antibodies against the programmed cell death protein-1 (anti-PD-1) in macroscopic stage III melanoma.

DOI: 10.1038/s41591-020-01211-7

Source: https://www.nature.com/articles/s41591-020-01211-7

Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
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