在晚期 HER2 阴性胃癌或胃食管交界处癌患者(pts)中,Ramucirumab 加紫杉醇作为转换维持治疗与继续奥沙利铂化疗的比较:ARMANI III 期试验。

IF 2.1 3区 工程技术 Q3 CHEMISTRY, MULTIDISCIPLINARY
F. Pietrantonio, G. Randon, S. Lonardi, S. Garattini, S. Tamberi, E. Giommoni, S. Di Donato, L. Fornaro, O. Brunetti, F. De Vita, G. Frassineti, Claudio Chini, A. Spallanzani, Valerie Bethaz, A. Strippoli, T. Latiano, Giovanni Gerardo Cardellino, Federica Palermo, Rosalba Miceli, M. Di Bartolomeo
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A sample size of 280 pts achieved a 90% power to detect as significant at a 5% level (2-sided log-rank test) a median PFS increase from 4 to 6 mos (target HR=0.67). HRs were estimated by Cox models adjusting for stratification factors. Restricted Mean Survival Time (RMST) analysis was conducted in case of violation of proportional hazards assumption. Results: From Jan 2017 to Oct 2023, 280 patients were randomly assigned (144 arm A/136 arm B). Baseline characteristics were: male sex 67/61%, median age 64/66 years, PS 0 74/65%, GEJ 26/26%, prior gastrectomy 28/23%, peritoneal metastases 53/42%. At a median follow-up of 43.7 months (IQR 22.0-57.9), median PFS was 6.6 vs. 3.5 mos in Arm A vs. B (HR=0.63, 95%CI 0.49-0.81; P<0.001). 24-mos RMST analysis showed a statistically significant 2.4-mos average increment (p=0.002). Median OS was 12.6 vs. 10.4 mos in Arm A vs. B (HR=0.75, 95%CI 0.58-0.97; P=0.030). 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引用次数: 0

摘要

LBA4002 背景:对于 HER2 阴性、PD-L1 低表达/无表达的晚期胃癌/胃癌患者,铂/氟嘧啶双药是标准的一线疗法。在这一患者群体中,治疗效果并不理想,仅有40%的临床试验患者接受了二线治疗。换药巩固维持治疗可延长初始策略的疗效并延缓临床恶化。尽管雷莫芦单抗在一线治疗中未能延长无进展生存期(PFS)和总生存期(OS),但紫杉醇联合雷莫芦单抗是一种标准的二线疗法,值得作为诱导后策略进行研究。研究方法将HER2阴性晚期胃癌/GEJ癌患者按原发部位(GEJ vs 胃)、既往胃切除术和腹膜疾病分层,随机分为1:A组)vs CAPOX/FOLFOX,剂量与上一个诱导周期相同,再进行3个月的治疗,然后使用氟嘧啶单药维持治疗(B组)。主要终点是 PFS,次要终点是 OS,同时还对生活质量、安全性和生物标志物进行了评估。280名患者的样本量达到了90%的检测能力,即在5%的水平上(双侧对数秩检验)检测到中位PFS从4个月增加到6个月(目标HR=0.67)具有显著性。HRs通过调整分层因素的Cox模型估算。如果违反比例危险假设,则进行限制平均生存时间(RMST)分析。结果:2017年1月至2023年10月,280名患者被随机分配(A/A组144人,B组136人)。基线特征为:男性67/61%,中位年龄64/66岁,PS 0 74/65%,GEJ 26/26%,既往胃切除术28/23%,腹膜转移53/42%。中位随访时间为 43.7 个月(IQR 22.0-57.9),A 组与 B 组的中位 PFS 分别为 6.6 个月和 3.5 个月(HR=0.63,95%CI 0.49-0.81;P<0.001)。24 个月 RMST 分析显示,平均增量为 2.4 个月,具有统计学意义(P=0.002)。A臂与B臂的中位OS分别为12.6个月与10.4个月(HR=0.75,95%CI 0.58-0.97;P=0.030)。A组与B组发生≥3级不良事件的频率分别为40.4%与20.7%,主要是中性粒细胞减少25.5/9.6%;发热性中性粒细胞减少2.1/0%;高血压6.4/0%;静脉血栓栓塞2.1/0%;周围神经病变5.7/6.7%。没有与治疗相关的死亡报告。结论对于HER2阴性的转移性胃癌/GEJ癌患者,根据特定指南和监管部门的批准,不符合初始免疫检查点抑制剂方案的患者,在奥沙利铂为基础的双药治疗3个月后换用紫杉醇加雷莫芦单抗维持治疗可能是一种新策略。临床试验信息:NCT02934464 .
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Ramucirumab plus paclitaxel as switch maintenance versus continuation of oxaliplatin-based chemotherapy in patients (pts) with advanced HER2-negative gastric or gastroesophageal junction (GEJ) cancer: The ARMANI phase III trial.
LBA4002 Background: In pts with HER2-negative advanced gastric/GEJ cancer and PD-L1 low/absent expression, platinum/fluoropyrimidine doublets are a standard first-line therapy. In this patient population, the outcomes are unsatisfactory and second-line therapy is given in only 40% of clinical trial patients. Switch consolidation maintenance may prolong the benefit of the initial strategy and delay clinical deterioration. Despite ramucirumab failing to prolong both progression-free survival (PFS) and overall survival (OS) in the first-line setting, paclitaxel plus ramucirumab is a standard second-line therapy and warrants investigation as a post-induction strategy. Methods: Pts with HER2-negative advanced gastric/GEJ cancer without disease progression after 3 months of initial oxaliplatin-based chemotherapy, stratified by site of origin (GEJ vs gastric), prior gastrectomy and peritoneal disease, were randomized 1:1 to ramucirumab 8 mg/Kg on days 1,15 plus paclitaxel 80 mg/sqm on days 1,8,15 every 28 days (arm A) vs CAPOX/FOLFOX at the same doses used in the last induction cycle, for additional 3 mos followed by fluoropyrimidine monotherapy maintenance (arm B). The primary endpoint was PFS, OS was a key secondary endpoint; quality of life, safety, and biomarkers were evaluated. A sample size of 280 pts achieved a 90% power to detect as significant at a 5% level (2-sided log-rank test) a median PFS increase from 4 to 6 mos (target HR=0.67). HRs were estimated by Cox models adjusting for stratification factors. Restricted Mean Survival Time (RMST) analysis was conducted in case of violation of proportional hazards assumption. Results: From Jan 2017 to Oct 2023, 280 patients were randomly assigned (144 arm A/136 arm B). Baseline characteristics were: male sex 67/61%, median age 64/66 years, PS 0 74/65%, GEJ 26/26%, prior gastrectomy 28/23%, peritoneal metastases 53/42%. At a median follow-up of 43.7 months (IQR 22.0-57.9), median PFS was 6.6 vs. 3.5 mos in Arm A vs. B (HR=0.63, 95%CI 0.49-0.81; P<0.001). 24-mos RMST analysis showed a statistically significant 2.4-mos average increment (p=0.002). Median OS was 12.6 vs. 10.4 mos in Arm A vs. B (HR=0.75, 95%CI 0.58-0.97; P=0.030). The frequency of grade ≥3 adverse events was 40.4% vs. 20.7% in arms A vs. B, respectively, mainly neutropenia 25.5/9.6%; febrile neutropenia 2.1/0%; hypertension 6.4/0%; venous thromboembolism 2.1/0%; peripheral neuropathy 5.7/6.7%. No treatment-related deaths were reported. Conclusions: Switch maintenance with paclitaxel plus ramucirumab after 3 months of oxaliplatin-based doublets may be a new strategy in patients with HER2-negative metastatic gastric/GEJ cancer who are non-eligible for initial immune checkpoint inhibitor-based regimens according to specific guidelines and regulatory approvals. Clinical trial information: NCT02934464 .
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来源期刊
Journal of Chemical & Engineering Data
Journal of Chemical & Engineering Data 工程技术-工程:化工
CiteScore
5.20
自引率
19.20%
发文量
324
审稿时长
2.2 months
期刊介绍: The Journal of Chemical & Engineering Data is a monthly journal devoted to the publication of data obtained from both experiment and computation, which are viewed as complementary. It is the only American Chemical Society journal primarily concerned with articles containing data on the phase behavior and the physical, thermodynamic, and transport properties of well-defined materials, including complex mixtures of known compositions. While environmental and biological samples are of interest, their compositions must be known and reproducible. As a result, adsorption on natural product materials does not generally fit within the scope of Journal of Chemical & Engineering Data.
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