Frontier Science for Cancer and Chemotherapy, Osaka University Graduate School of Medicine, Suita, Japan.
Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea.
Gastric Cancer. 2020 Jan;23(1):143-153. doi: 10.1007/s10120-019-00970-8. Epub 2019 May 13.
Data on immune checkpoint inhibitor efficacy in patients with human epidermal growth factor receptor 2-positive (HER2+) advanced gastric/gastroesophageal junction (G/GEJ) cancer are lacking. Because HER2 status was not captured in the ATTRACTION-2 trial, we used patients with prior trastuzumab use (Tmab+) as surrogate for HER2 expression status to evaluate the efficacy and safety of nivolumab as third- or later-line therapy in these patients.
In ATTRACTION-2, a randomized, double-blind, placebo-controlled, phase 3 multicenter trial, patients were randomized (2:1) to receive nivolumab (3 mg/kg) or placebo every 2 weeks until disease progression or toxicity requiring study discontinuation. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and safety were assessed.
Of 493 enrolled patients, 81 (nivolumab, n = 59; placebo, n = 22) were Tmab+ and 412 (nivolumab, n = 271; placebo, n = 141) were Tmab-. In both groups, patients receiving nivolumab showed a longer median OS vs placebo (Tmab+, 8.3 [95% confidence interval, 5.3-12.9] vs 3.1 [1.9-5.3] months, hazard ratio, 0.38 [0.22-0.66]; P = 0.0006; Tmab-, 4.8 [4.1-6.0] vs 4.2 [3.6-4.9] months, 0.71 [0.57-0.88]; P = 0.0022). PFS was longer in both groups receiving nivolumab vs placebo (Tmab+, 1.6 [1.5-4.0] vs 1.5 [1.3-2.9] months, 0.49 [0.29-0.85]; P = 0.0111; Tmab-, 1.6 [1.5-2.4] vs 1.5 [1.5-1.5] months, 0.64 [0.51-0.80]; P = 0.0001).
Nivolumab was efficacious and safe as third- or later-line therapy regardless of prior trastuzumab use in patients with advanced G/GEJ cancer.
缺乏人表皮生长因子受体 2 阳性（HER2+）晚期胃/胃食管交界处（G/GEJ）癌症患者接受免疫检查点抑制剂疗效的数据。由于 ATTRACTION-2 试验中未捕获 HER2 状态，我们使用先前使用曲妥珠单抗（Tmab+）的患者作为 HER2 表达状态的替代指标，以评估纳武利尤单抗作为三线或后线治疗在这些患者中的疗效和安全性。
在 ATTRACTION-2 中，这是一项随机、双盲、安慰剂对照、多中心 3 期临床试验，患者按 2:1 比例随机分配（纳武利尤单抗，n=59；安慰剂，n=22）接受纳武利尤单抗（3mg/kg）或安慰剂，每 2 周一次，直至疾病进展或因毒性而需要停止研究。评估总生存期（OS）、无进展生存期（PFS）、客观缓解率（ORR）和安全性。
在 493 名入组患者中，81 名（纳武利尤单抗，n=59；安慰剂，n=22）为 Tmab+，412 名（纳武利尤单抗，n=271；安慰剂，n=141）为 Tmab-。在两组中，接受纳武利尤单抗的患者的中位 OS 均长于安慰剂（Tmab+，8.3[95%置信区间，5.3-12.9] vs 3.1[1.9-5.3]个月，风险比，0.38[0.22-0.66]；P=0.0006；Tmab-，4.8[4.1-6.0] vs 4.2[3.6-4.9]个月，0.71[0.57-0.88]；P=0.0022）。两组接受纳武利尤单抗的患者的 PFS 均长于安慰剂（Tmab+，1.6[1.5-4.0] vs 1.5[1.3-2.9]个月，0.49[0.29-0.85]；P=0.0111；Tmab-，1.6[1.5-2.4] vs 1.5[1.5-1.5]个月，0.64[0.51-0.80]；P=0.0001）。
纳武利尤单抗作为三线或后线治疗在晚期 G/GEJ 癌症患者中无论先前是否使用过曲妥珠单抗，均有效且安全。
