摘要目的 回顾性分析信迪利单抗联合化疗一线治疗晚期胃癌或胃食管结合部腺癌的疗效。方法 收集2019-01至2022-10解放军总医院第一医学中心收治的信迪利单抗联合化疗一线治疗晚期胃癌或胃食管结合部腺癌患者临床资料,分析入组患者中位无进展生存期(mPFS)、客观缓解率(ORR)及疾病控制率(DCR)。结果 共纳入71例患者,中位年龄60岁,男53例,女18例,其中45例给予信迪利联合以奥沙利铂为基础方案的治疗,26例给予信迪利联合以紫杉醇(白蛋白结合型)为基础方案的治疗。全组患者的ORR为67.6%,DCR为97.2%,mPFS为11.2个月(95% CI 9.7~12.8)。联合奥沙利铂为基础方案组的ORR为73.3%,DCR为97.8%,mPFS为11.3个月(95% CI 5.5~17.2)。联合紫杉醇(白蛋白结合型)为基础方案组的ORR为57.7%,DCR为96.2%,mPFS为10.9个月(95% CI 9.0~12.9),两组ORR及mPFS差异无统计学意义。结论 在晚期胃癌或胃食管结合部腺癌中,一线应用信迪利单抗联合化疗,患者无进展生存期明显获益。信迪利单抗联合以紫杉醇(白蛋白结合型)为基础的治疗组疗效与联合以奥沙利铂为基础治疗组相当。
Abstract：Objective To retrospectively analyze the efficacy of sintilimab combined with chemotherapy in the first-line treatment of advanced gastric or gastroesophageal junction adenocarcinoma(GC or GEJC). Methods Clinical data of patients with advanced GC or GEJC who received first-line sintilimab combined with chemotherapy at the First Medical Center of the Chinese PLA General Hospital from January 2019 to October 2022 were collected. Median progression-free survival (mPFS), objective response rate (ORR), and disease control rate (DCR) of enrolled patients were retrospectively analyzed. Results A total of 71 patients were included, with a median age of 60, including 53 males and 18 females. Forty-five patients were treated with sintilimab combined with oxaliplatin based regimen, while 26 patients were treated with sintilimab combined with albumin-bound paclitaxel (nab-paclitaxel) based regimen. The ORR, DCR and mPFS of all patients were 67.6%, 97.2% and 11.2 months (95% CI 9.7-12.8), respectively. The ORR, DCR and mPFS of oxaliplatin-based combination group were 73.3%, 97.8% and 11.3 months (95%CI 5.5-17.2), while the ORR, DCR and mPFS of nab-paclitaxel-based combination group were 57.7%, 96.2% and 10.9 months (95%CI 9.0-12.9). There was no significant difference in ORR and PFS between the two groups. Conclusions The first-line application of sintilimab combined with chemotherapy in advanced GC or GEJC can significantly benefit the mPFS of patients. In addition, the efficacy of sintilimab combined with nab-paclitaxel-based treatment is comparable with that with oxaliplatin-based treatment.
李娟, 叶斯斯, 张鹏飞, 白莉. 信迪利单抗一线治疗晚期胃癌或胃食管结合部腺癌的疗效分析[J]. 武警医学, 2023, 34(6): 476-480.
LI Juan, YE Sisi, ZHANG Pengfei, BAI Li. Efficacy of sintilimab combined with chemotherapy in the first-line treatment of advanced gastric cancer or gastroesophageal junction adenocarcinoma. Med. J. Chin. Peop. Armed Poli. Forc., 2023, 34(6): 476-480.
Sung H, Ferlay J, Siegel R L, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries[J]. CA Cancer J Clin, 2021,71(3): 209-249.
[2]
Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries?[J]. Lancet Glob Health, 2018,6(5): e555-e567.
[3]
Janjigian Y Y, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial?[J]. Lancet, 2021,398(10294): 27-40.
[4]
Xu J, Jiang H, Pan Y, et al. LBA53 Sintilimab plus chemotherapy (chemo) versus chemo as first-line treatment for advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma (ORIENT-16): First results of a randomized, double-blind, phase Ⅲ study?[J]. Annals of Oncology, 2021,32: S1331.
[5]
Boku N, Ryu M H, Kato K, et al. Safety and efficacy of nivolumab in combination with S-1/capecitabine plus oxaliplatin in patients with previously untreated, unresectable, advanced, or recurrent gastric/gastroesophageal junction cancer: interim results of a randomized, phase II trial (ATTRACTION-4) [J]. Ann Oncol, 2019,30(2): 250-258.
[6]
Shitara K, Cutsem E, Bang Y J, et al. Efficacy and safety of pembrolizumab or pembrolizumab plus chemotherapy vs chemotherapy alone for patients with first-line, advanced gastric cancer: the KEYNOTE-062 phase 3 randomized clinical trial[J]. JAMA Oncol, 2020, 6(10):1571-1580.
[7]
Sun J M, Shen L, Shah M A, et al. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study[J]. Lancet, 2021, 398(10302): 759-771.
[8]
Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer[J]. N Engl J Med, 2006,355(24): 2542-2550.
[9]
Miller K, Wang M, Gralow J, et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer[J]. N Engl J Med, 2007,357(26): 2666-2676.
[10]
Ozols R F, Bundy B N, Greer B E, et al. Phase Ⅲ trial of carboplatin and paclitaxel compared with cisplatin and paclitaxel in patients with optimally resected stage Ⅲ ovarian cancer: a Gynecologic Oncology Group study[J]. J Clin Oncol, 2003,21(17): 3194-3200.
[11]
Dai Y H, Yu X J, Xu H T, et al. Nab-paclitaxel plus S-1 versus oxaliplatin plus S-1 as first-line treatment in advanced gastric cancer: results of a multicenter, randomized, phase Ⅲ trial (GAPSO study)[J]. Ther Adv Med Oncol, 2022,14: 17588359221118020.
[12]
Högner A, Breithaupt K, Stein A, et al. RAP: a phase Ⅱ trial with ramucirumab, avelumab, and paclitaxel as second line treatment in gastro-esophageal adenocarcinoma of the arbeitsgemeinschaft internistische onkologie (AIO)[J]. J Clin Oncol, 2019, 37(15_suppl): TPS4148-TPS4148.
[13]
Liu T, Bai Y, Lin X, et al. First-line nivolumab plus chemotherapy vs chemotherapy in patients with advanced gastric, gastroesophageal junction and esophageal adenocarcinoma: CheckMate 649 Chinese subgroup analysis[J]. Int J Cancer, 2023, 152(4): 749-760.
[14]
Janjigian Y Y, Kawazoe A, Yanez P E, et al. Pembrolizumab plus trastuzumab and chemotherapy for HER2+ metastatic gastric or gastroesophageal junction (G/GEJ) cancer: Initial findings of the global phase 3 KEYNOTE-811 study[J].J Clin Oncol, 2021, 39(15_suppl): 4013.
[15]
Chen L T, Satoh T, Ryu M H, et al. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data[J]. Gastric Cancer, 2020,23(3): 510-519.
[16]
Kang Y K, Chen L T, Ryu M H, et al. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial[J]. Lancet Oncol, 2022,23(2): 234-247.
[17]
Wang F, Wei X L, Wang F H, et al. Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432[J]. Ann Oncol, 2019,30(9): 1479-1486.
[18]
Jiang H, Yu X, Li N, et al. 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[J]. J Immunother Cancer, 2022, 10(3).1365-1368.
[19]
Guo H, Ding P, Sun C, et al. Efficacy and safety of sintilimab plus XELOX as a neoadjuvant regimen in patients with locally advanced gastric cancer: a single-arm, open-label, phase Ⅱ trial?[J]. Front Oncol, 2022,12: 927781.
[20]
He M M, Wang F, Jin Y, et al. Phase II clinical trial of S-1 plus nanoparticle albumin-bound paclitaxel in untreated patients with metastatic gastric cancer?[J]. Cancer Sci, 2018,109(11): 3575-3582.
[21]
Peng Z, Wei J, Wang F, et al. Camrelizumab Combined with Chemotherapy Followed by Camrelizumab plus Apatinib as First-line Therapy for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma[J]. Clin Cancer Res, 2021,27(11): 3069-3078.
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