编者按：意大利米兰国家癌症研究所的肿瘤内科医生Filippo Pietrantonio在2024年美国临床肿瘤学会（ASCO）年会上报告了Ⅲ期试验ARMANI的结果，该研究同时入选本次年会的口头摘要会议（Oral Abstract Session）和最新突破摘要（Late Breaking Abstract，LBA）专场。在大会现场，Dr.Pietrantonio为我们详细阐析了ARMANI试验的结果和临床指导意义。

《肿瘤瞭望-消化时讯》：ARMANI的首批结果在2024年ASCO上发布。根据研究结果，转换雷莫西尤单抗联合紫杉醇作为晚期HER2阴性胃或食管胃交界处(GEJ)癌的维持治疗疗效如何？

Dr Pietrantonio: Thank you for the question. My name is Filippo Pietrantonio. I am a medical oncologist from the National Cancer Institute of Milan, Italy. Here at ASCO 2024, I presented the results of the ARMANI phase Ⅲ trial. This trial was conducted in Italy. It is a multicenter trial, and we investigated switch maintenance with paclitaxel plus ramucirumab versus continuation of oxaliplatin-based first-line chemotherapy in patients with HER2-negative advanced gastric or gastroesophageal junction cancer. A little bit of background of the trial, we know first-line doublet chemotherapy with platinum/fluoropyrimidine agents is standard-of-care in first-line therapy in HER2-negative disease and low or absent PD-L1 expression. This is because the addition of immune checkpoint inhibitors is not approved or recommended in several countries, and we believe outcomes for this special patient population should be improved. The chance of receiving an active second-line therapy is low - around 40-50% - even in clinical trials. We also know the addition of ramucirumab to first-line cisplatin/fluoropyrimidine chemotherapy failed in the first-line setting, however, the addition of ramucirumab to paclitaxel is still a standard-of-care in the second-line setting. Many trials investigated whether switch maintenance or so-called early second-line with paclitaxel and ramucirumab was superior to continuation of first-line oxaliplatin-based chemotherapy. The trial enrolled 280 patients with HER2-negative disease. The primary endpoint of the study was progression-free survival. These patients had their disease controlled after 12 weeks of CAPOX/FOLFOX, and the primary endpoint of the study was met, with patients on paclitaxel and ramucirumab showing significantly improved progression-free survival. PFS was 3.5 months in the control arm, and 6.6 months in the experimental arm. The hazard ratio was 0.64. Also, overall survival was a secondary endpoint, and was significantly improved as well in patients receiving ramucirumab plus paclitaxel. The median overall survival was 10.4 months in the control arm, and 12.6 months in the experimental arm. Again, this was statistically significant with a hazard ratio of 0.75. The safety profile of paclitaxel plus ramucirumab was consistent with the literature, with no new safety signals. So based on the results of the ARMANI trial, this may be a new standard post-induction strategy, at least nowadays, in patients who are not eligible for upfront therapy with immune checkpoint inhibitors.

Dr Pietrantonio: We know that the treatment algorithm in this disease is changing rapidly. Nowadays, we have immune checkpoint inhibitors approved. Depending on the country, these agents are approved in all comers, or in Europe, in patients with high PD-L1 expression. We will soon have other agents also, such as Claudin-18.2 targeting agents with some monoclonal antibodies, such as zolbetuximab. The ARMANI strategy will be possible for patients who are not eligible for upfront therapy with novel agents such as monoclonal antibodies, with upfront chemotherapy alone.

Dr.Pietrantonio：2024 ASCO年会是胃癌领域的一次隆重盛会，有很多新的试验数据发布，如在欧洲德国进行的RENAISSANCE试验等。局限性转移性胃癌患者的治疗模式变化迅速，大会公布了很多新辅助免疫治疗及其他重要的试验数据。刚刚结束的全体会议公布了ESOPEC Ⅲ期试验结果，该试验比较了FLOT与CROSS方案在食管腺癌患者中的疗效，该试验表明 FLOT 化疗的总生存获益呈阳性，因此关于该疾病最佳治疗方案的长期争论可能最终以 FLOT 为赢家而结束。