Background: The randomized phase III RAINBOW trial established paclitaxel (pac) plus ramucirumab (ram) as a global standard for second-line (2L) therapy in advanced gastric and gastroesophageal junction adenocarcinoma, together gastroesophageal adenocarcinoma (GEA). Patients (pts) receiving first-line (1L) FOLFOX often develop neuropathy that renders continued neurotoxic agents in the 2L setting unappealing and other regimens more desirable. As such, FOLFIRI-ram has become an option for patients with 2L GEA. FOLFIRI-ramucirumab (ram) has demonstrated safety and activity in 2L colorectal cancer, but efficacy/safety data in GEA are lacking.
Subjects, materials, and methods: Patients with GEA treated with 2L FOLFIRI-ram between August 2014 and April 2018 were identified. Clinicopathologic data including oxaliplatin neurotoxicity rates/grades (G), 2L treatment response, progression-free survival (PFS), overall survival (OS), safety, and molecular features were abstracted from three U.S. academic institutions. Kaplan-Meier survival analysis was used to generate PFS/OS; the likelihood ratio test was used to determine statistical significance.
Results: We identified 29 pts who received 2L FOLFIRI-ram. All pts received 1L platinum + fluoropyrimidine, and 23 of 29 (79%) had post-1L neuropathy; 12 (41%) had G1, and 11 (38%) had G2. Patients were evenly split between esophagus/gastroesophageal junction (12; 41%) and gastric cancer (17; 59%). Among evaluable pts (26/29), the overall response rate was 23% (all partial response) with a disease control rate of 79%. Median PFS was 6.0 months and median OS was 13.4 months among all evaluable pts. Six- and 12-month OS were 90% (n = 18/20) and 41% (n = 7/17). There were no new safety signals.
Conclusion: We provide the first data suggesting FOLFIRI-ram is a safe, non-neurotoxic regimen comparing favorably with the combination of pac + ram used in the seminal RAINBOW trial.
Implications for practice: Results of this study provide initial support for the safety and efficacy of second-line (2L) FOLFIRI-ramucirumab (ram) after progression on first-line platinum/fluoropyrimidine in patients with gastroesophageal adenocarcinoma (GEA). The overall response, progression-free survival, overall survival, and toxicity profile compare favorably with paclitaxel (pac) + ram and highlight the importance of the ongoing phase II RAMIRIS trial examining FOLFIRI-ram versus pac + ram in 2L GEA (NCT03081143). FOLFIRI-ram may warrant consideration for inclusion as an alternate regimen in consensus guidelines for GEA.
摘要
背景。随机 III 期 RAINBOW 试验制定了紫杉醇 (pac) 和雷莫芦单抗 (ram) 作为晚期胃部和胃食管结合部腺癌，统称为胃食管腺癌 (GEA)，二线 (2L) 治疗的全球标准。接受一线 (1L) FOLFOX 治疗的患者 (pt) 通常会出现神经病变，这使得在 2L 环境中持续使用神经毒剂不具吸引力，而其他疗法则更为可取。因此，FOLFIRI‐雷莫芦单抗 (ram) 成为 2L GEA 患者的一种选择。FOLFIRI‐ ram已在 2L 结直肠癌治疗中显示出安全性和活性，但是，在 GEA 治疗中尚缺乏有效性/安全性数据。
受试者、材料和方法。我们找出在 2014 年 8 月至 2018 年 4 月期间接受 2L FOLFIRI‐ram 治疗的 GEA 患者。从三个美国学术机构中提取包括奥沙利铂神经毒性率/等级 (G)、2L 治疗反应、无进展生存期 (PFS)、总生存期 (OS)、安全性以及分子特性在内的临床病理数据。Kaplan‐Meier 生存分析用于生成 PFS/OS；似然比检验用于确定统计显著性。
结果。我们找到 29 名接受 2L FOLFIRI‐ram 治疗的患者。所有患者均接受 1L 铂类 + 氟尿嘧啶类治疗，29 名患者中的 23 名患者 (79%) 出现 1L 后神经病变；12 名患者 (41%) 为 G1，11 名患者 (38%) 为 G2。患者均匀地分布于食道/胃食管结合部癌症(12 名患者；41%)和胃癌(17 名患者；59%)之间。在可评价的患者(29 名患者中的 26 名患者)中，总缓解率为 23%(全部为部分缓解)，疾病控制率为 79%。在所有可评价的患者中，中位 PFS 为 6.0 个月，中位 OS 为 13.4 个月。6 个月 OS 和 12 个月 OS 分别占 90% (n = 18/20) 和 41% (n = 7/17)。没有新的安全信号。
结论。我们提供了首个数据表明 FOLFIRI‐ram 是一种不会毒害神经的安全疗法，可以与创新性 RAINBOW 试验中使用的 pac + ram 联合治疗相媲美。
实践意义:本研究结果对胃食管腺癌 (GEA) 患者在一线铂类/氟尿嘧啶类治疗出现进展后的二线 (2L) FOLFIRI‐雷莫芦单抗(ram) 治疗提供初步支持。总体反应、无进展生存期、总生存期以及毒性特征可以与紫杉醇 (pac) + ram 相媲美，并强调了旨在于 2L GEA (NCT03081143) 中检验 FOLFIRI‐ram 对比 pac + ram 的正在进行的 II 期 RAMIRIS 试验的重要性。可能值得考虑的是，将 FOLFIRI‐ram 作为一种替代疗法列入 GEA 的共识指南。
Keywords: FOLFIRI; GEJ adenocarcinoma; Gastric cancer; Ramucirumab; Second line.
© AlphaMed Press 2018.