Efficacy and safety of neoadjuvant sintilimab, oxaliplatin and capecitabine in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: early results of a phase 2 study.
Efficacy and safety of neoadjuvant sintilimab, oxaliplatin and capecitabine in patients with locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma: early results of a phase 2 study.
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DOI：
10.1136/jitc-2021-003635
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发表时间：
2022-03
影响因子：
10.9
通讯作者：
Teng L
中科院分区：
文献类型：
--
作者：
Jiang H;Yu X;Li N;Kong M;Ma Z;Zhou D;Wang W;Wang H;Wang H;He K;Li Z;Lu Y;Zhang J;Zhao K;Zhang Y;Xu N;Li Z;Liu Y;Wang Y;Wang Y;Teng L
免疫检查点抑制剂极大地改善了各种晚期恶性肿瘤的预后，包括胃和胃食管交界处（G/GEJ）癌。然而，抗程序性细胞死亡蛋白-1治疗在新辅助治疗中的作用尚不清楚。这项2期研究旨在评估sintilimab + CapeOx作为晚期可切除G/GEJ腺癌患者的新辅助方案。入选符合条件的可切除G/GEJ腺癌cT3-4NanyM0期患者。患者接受新辅助治疗：辛替单抗（<60 kg患者3 mg/kg，≥60 kg患者200 mg，第1天）+ CapeOx （D1为奥沙利铂130 mg/m2， D1 - d14为卡培他滨1000 mg/m2，每天2次），每21天，手术切除前3个周期，手术切除后同样剂量的CapeOx辅助治疗3个周期。主要终点为病理完全缓解（pCR）率。次要终点包括客观缓解率、肿瘤消退等级（Becker标准）、生存和安全性。截至2020年7月30日，共有36名患者入组。GEJ癌7例（19.4%），临床ⅲ期34例（94.4%）。共有35例（97.2%）患者完成了3个周期的新辅助治疗，1例患者因不良事件接受了2个周期的新辅助治疗。所有患者均行手术治疗，R0切除率为97.2%。本研究中，分别有7例（19.4%,95% CI: 8.8% ~ 35.7%; 90% CI: 10.7% ~ 33.1%）和17例（47.2%,95% CI: 31.6% ~ 64.3%）患者获得了pCR和主要病理反应。31例患者接受辅助治疗。截至2021年12月20日，3例患者复发死亡，2例患者复发存活。中位无病生存期（DFS）和总生存期（OS）均未达到。1年DFS和OS率分别为90.3% （95% CI: 80.4% ~ 100.0%）和94.1% （95% CI: 86.5% ~ 100.0%）。在新辅助治疗期间，最常见的（bbb1患者）3级治疗相关不良事件是贫血和中性粒细胞减少症（n=5, 13.9%）。未观察到严重不良事件（ae）或4-5级ae。辛替单抗联合奥沙利铂/卡培他滨在新辅助治疗中显示出良好的疗效，具有令人鼓舞的pCR率和良好的安全性。这种联合方案可能为局部晚期可切除的G/GEJ腺癌患者提供新的选择。试验注册;NCT04065282。
Immune checkpoint inhibitors have greatly improved the prognoses of diverse advanced malignancies, including gastric and gastroesophageal junction (G/GEJ) cancer. However, the role of anti-programmed cell death protein-1 treatment in the neoadjuvant setting remains unclear. This phase 2 study aimed to evaluate sintilimab plus CapeOx as a neoadjuvant regimen in patients with advanced resectable G/GEJ adenocarcinoma. Eligible patients with resectable G/GEJ adenocarcinoma stage cT3-4NanyM0 were enrolled. Patients received neoadjuvant treatment with sintilimab (3 mg/kg for cases <60 kg or 200 mg for those ≥60 kg on day 1) plus CapeOx (oxaliplatin at 130 mg/m2 on D1 and capecitabine at 1000 mg/m2 two times per day on D1–D14) every 21 days, for three cycles before surgical resection, followed by adjuvant treatment with three cycles of CapeOx with the same dosages after surgical resection. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included objective response rate, tumor regression grade per Becker criteria, survival and safety. As of July 30, 2020, 36 patients were enrolled. Totally 7 (19.4%) patients had GEJ cancer, and 34 (94.4%) patients were clinical stage III cases. A total of 35 (97.2%) patients completed three cycles of neoadjuvant treatment, and 1 patients received two cycles due to adverse events. All patients underwent surgery and the R0 resection rate was 97.2%. In this study, pCR and major pathological response were achieved in 7 (19.4%, 95% CI: 8.8% to 35.7%; 90% CI: 10.7% to 33.1%) and 17 (47.2%, 95% CI: 31.6% to 64.3%) patients, respectively. Thirty-one patients received adjuvant treatment. By December 20, 2021, three patients died after disease relapse, and two patients were alive with relapse. Median disease-free survival (DFS) and overall survival (OS) were not reached. The 1-year DFS and OS rates were 90.3% (95% CI: 80.4% to 100.0%) and 94.1% (95% CI: 86.5% to 100.0%), respectively. The most common (>1 patient) grade 3 treatment-related adverse events during neoadjuvant treatment were anemia and neutropenia (n=5 each, 13.9%). No serious adverse events (AEs) or grade 4–5 AEs were observed. Sintilimab plus oxaliplatin/capecitabine showed promising efficacy with encouraging pCR rate and good safety profile in the neoadjuvant setting. This combination regimen might present a new option for patients with locally advanced, resectable G/GEJ adenocarcinoma. Trial registration; NCT04065282.
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DOI：
10.1016/s1470-2045(13)70334-6
发表时间：
2014-01
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Hellmann MD;Chaft JE;William WN Jr;Rusch V;Pisters KM;Kalhor N;Pataer A;Travis WD;Swisher SG;Kris MG;University of Texas MD Anderson Lung Cancer Collaborative Group
通讯作者：
University of Texas MD Anderson Lung Cancer Collaborative Group
影响因子：
28.4
作者：
Shitara, Kohei;Van Cutsem, Eric;Tabernero, Josep
通讯作者：
Tabernero, Josep
影响因子：
45.3
作者：
Schuhmacher, Christoph;Gretschel, Stephan;Schlag, Peter M.
通讯作者：
Schlag, Peter M.
影响因子：
3.8
作者：
D'Ugo, D.;Persiani, R.;Ricci, R.
通讯作者：
Ricci, R.
DOI：
10.1016/j.jtho.2018.05.004
发表时间：
2018-11
期刊：
Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
影响因子：
--
作者：
Spigel DR;Chaft JE;Gettinger S;Chao BH;Dirix L;Schmid P;Chow LQM;Hicks RJ;Leon L;Fredrickson J;Kowanetz M;Sandler A;Funke R;Rizvi NA
通讯作者：
Rizvi NA