Randon Giovanni, Lonardi Sara, Fassan Matteo, Palermo Federica, Tamberi Stefano, Giommoni Elisa, Ceccon Carlotta, Di Donato Samantha, Fornaro Lorenzo, Brunetti Oronzo, De Vita Ferdinando, Bittoni Alessandro, Chini Claudio, Spallanzani Andrea, Nappo Floriana, Bethaz Valerie, Strippoli Antonia, Latiano Tiziana, Cardellino Giovanni Gerardo, Giuliani Francesco, Morano Federica, Niger Monica, Raimondi Alessandra, Prisciandaro Michele, Pircher Chiara Carlotta, Sciortino Carolina, Marchesi Silvia, Garattini Silvio Ken, Airò Giulia, Miceli Rosalba, Di Bartolomeo Maria, Pietrantonio Filippo
Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Department of Oncology, Veneto Institute of Oncology Istituto Oncologico Veneto-IRCCS, Padua, Italy.
Lancet Oncol. 2024 Dec;25(12):1539-1550. doi: 10.1016/S1470-2045(24)00580-1. Epub 2024 Nov 15.
Paclitaxel plus ramucirumab is recommended as a second-line treatment regimen in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer. We aimed to assess whether switch maintenance or early second-line therapy with paclitaxel plus ramucirumab improved outcomes compared with continuation of oxaliplatin and fluoropyrimidine doublet chemotherapy as a first-line strategy.
ARMANI was a multicentre, open-label, randomised, phase 3 trial done in 31 hospitals in Italy. We enrolled patients aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0 or 1 and locally advanced unresectable or metastatic HER2-negative gastric or gastro-oesophageal junction cancer, who had disease control after 3 months of FOLFOX (leucovorin, fluorouracil, and oxaliplatin) or CAPOX (capecitabine and oxaliplatin). Patients were randomly assigned (1:1) to either paclitaxel 80 mg/m on days 1, 8, and 15 plus ramucirumab at 8 mg/kg on days 1 and 15 every 28 days intravenously (switch maintenance group) or continuation of oxaliplatin-based doublet chemotherapy (FOLFOX or CAPOX) for an additional 12 weeks, followed by fluoropyrimidine monotherapy maintenance (control group). Randomisation was stratified by previous gastrectomy (no vs yes), peritoneal carcinomatosis (yes vs no), and primary tumour location (gastro-oesophageal junction vs gastric). Treatment group allocation was done using a web-based system with a minimisation algorithm implementing a random component. The primary endpoint was progression-free survival, analysed on an intention-to-treat basis. The safety population included patients who received at least one dose of the study treatment. This study is registered with ClinicalTrials.gov, NCT02934464, and is complete.
Between Jan 1, 2017, and Oct 2, 2023, 280 patients were randomly assigned to receive paclitaxel plus ramucirumab (switch maintenance group; n=144) or to continue FOLFOX or CAPOX (control group; n=136). All patients were White. 180 (64%) of 280 patients were male and 100 (36%) were female. At a median follow-up of 43·7 months (IQR 24·0-57·9), 253 (90%) of 280 patients had a progression-free survival event: 131 (91%) of 144 patients in the switch maintenance group and 122 (90%) of 136 patients in the control group. Median progression-free survival was 6·6 months (95% CI 5·9-7·8) in the switch maintenance group and 3·5 months (2·8-4·2) in the control group (HR 0·61, 95% CI 0·48-0·79; p=0·0002). The assumption of proportional hazards was violated; in an analysis of 24-month restricted mean survival time, restricted mean progression-free survival was 8·8 months (95% CI 7·7-9·9) in the switch maintenance group and 6·1 months (5·0-7·2) in the control group (p=0·0010). The most frequent grade 3-4 treatment-related adverse events were neutropenia (37 [26%] patients in the switch maintenance group vs 13 [10%] patients in the control group), peripheral neuropathy (eight [6%] vs nine [7%]) and arterial hypertension (nine [6%] vs none). Serious adverse events occurred in 28 (20%) of 141 patients in the experimental group and 15 (11%) of 135 patients in the control group; these events were treatment-related in two (1%) patients in the switch maintenance group (pulmonary embolism) and two (1%) patients in the control group (mucositis and anaemia). No treatment-related deaths occurred.
Paclitaxel and ramucirumab switch maintenance could be a potential treatment strategy in patients with advanced HER2-negative gastric or gastro-oesophageal junction cancer who are not eligible for immunotherapy or targeted agents.
Partly funded by Eli Lilly.
对于晚期人表皮生长因子受体2（HER2）阴性胃癌或胃食管交界癌患者，紫杉醇联合雷莫西尤单抗被推荐作为二线治疗方案。我们旨在评估，相较于继续使用奥沙利铂和氟嘧啶双联化疗作为一线治疗策略，改用紫杉醇联合雷莫西尤单抗进行维持治疗或早期二线治疗是否能改善患者预后。
ARMANI是一项在意大利31家医院开展的多中心、开放标签、随机3期试验。我们纳入了年龄在18岁及以上、东部肿瘤协作组体能状态为0或1、局部晚期不可切除或转移性HER2阴性胃癌或胃食管交界癌患者，这些患者在接受3个月的FOLFOX（亚叶酸钙、氟尿嘧啶和奥沙利铂）或CAPOX（卡培他滨和奥沙利铂）治疗后病情得到控制。患者被随机分配（1:1），每28天静脉注射一次，其中一组在第1、8和15天接受80mg/m²的紫杉醇，在第1和15天接受8mg/kg的雷莫西尤单抗（改用维持治疗组），另一组继续基于奥沙利铂的双联化疗（FOLFOX或CAPOX）12周，随后接受氟嘧啶单药维持治疗（对照组）。随机分组按既往是否行胃切除术（否vs是）、是否存在腹膜癌转移（是vs否）和原发肿瘤部位（胃食管交界vs胃）进行分层。治疗组分配通过基于网络的系统完成，该系统使用了带有随机成分的最小化算法。主要终点是无进展生存期，采用意向性分析。安全人群包括接受了至少一剂研究治疗的患者。本研究已在ClinicalTrials.gov注册，注册号为NCT02934464，现已完成。
在2017年1月1日至2023年10月2日期间，280例患者被随机分配接受紫杉醇联合雷莫西尤单抗治疗（改用维持治疗组；n = 144）或继续接受FOLFOX或CAPOX治疗（对照组；n = 136）。所有患者均为白人。280例患者中180例（64%）为男性，100例（36%）为女性。中位随访43.7个月（四分位间距24.0 - ）
