Risk Factors Predicting Outcomes in Advanced Upper Gastrointestinal Cancers Treated With Immune Checkpoint Inhibitors

被引：0
作者：
Manne, Ashish [1 ,2 ]
Tounkara, Fode [3 ]
Min, Eric [1 ,2 ]
Samuel, Paul [1 ,2 ]
Benson, Katherine [1 ,2 ]
Noonan, Anne M. [1 ,2 ]
Mittra, Arjun [1 ,2 ]
Hays, John [1 ,2 ]
Roychowdhury, Sameek [1 ,2 ]
Malalur, Pannaga [1 ,2 ]
Rahman, Shafia [1 ,2 ]
Jin, Ning [1 ,2 ]
Pitter, Kenneth [4 ]
Miller, Eric [4 ]
Diaz, Alexandra [4 ]
He, Kai [1 ,2 ]
机构：
[1] Ohio State Univ, Ctr Comprehens Canc, Arthur G James Canc Hosp, Div Med Oncol,Dept Internal Med, Columbus, OH 43210 USA
[2] Ohio State Univ, Richard J Solove Res Inst, Comprehens Canc Ctr, Columbus, OH 43210 USA
[3] Ohio State Univ, Dept Biostat, Columbus, OH USA
[4] Ohio State Univ, Comprehen s Canc Ctr, Dept Radiat Oncol, Columbus, OH 43210 USA
来源：
GASTROENTEROLOGY RESEARCH | 2024年 / 17卷 / 5-6期
关键词：
Immune checkpoint inhibitors; Esophageal cancer; Gas- tric cancer; Immunotherapy; Biomarkers; Prognostic marker; PEMBROLIZUMAB PLUS CHEMOTHERAPY; DOUBLE-BLIND; ESOPHAGEAL; NIVOLUMAB;
D O I：
10.14740/gr1768
中图分类号：
R57 [消化系及腹部疾病];
学科分类号：
摘要：
Background: Immune checkpoint inhibitors (ICIs) have moved to the frontline in recent years to manage upper gastrointestinal (UGI) tumors, such as esophageal and gastric cancers. This retrospective review sheds light on real-world data on ICI-treated UGI tumors to identify risk factors (clinical and pathological) impacting the outcome other than traditional biomarkers (programmed cell death ligand 1 (PD-L1) or microsatellite instability status). Methods: Patients with UGI tumors who received at least one dose of ICI for stage IV or recurrent disease between January 1, 2015, and July 31, 2021, at The Ohio State University were included in the study. The patients' baseline characteristics, labs, and blood counts (even at disease progression) were extracted with survival outcomes (progression-free survival (PFS) and overall survival (OS)). Descriptive statistics, log-rank test and Cox proportional hazard model for survival outcomes, Fisher exact test for categorical variables, were conducted using JMP Pro 16 (SAS Institute Inc., Cary, NC). Results: We had 64 patients (84% males) included in the study, with the racial distribution as follows: 88% Caucasian, 5%AfricanAmeri- can, 1% Asian, and 6% from other racial groups. Men and the use of ICI in third lines or more had a positive impact on PFS and OS. For OS, 1) history of surgery positively impacted the outcome, while bone metastases worsened it; 2) baseline red blood cell count (RBC), hemoglobin, and thyroid-stimulating hormone (TSH) negatively impacted the OS. For PFS, 1) PD-L1 positivity, baseline lymphocyte count, and aspartate transferase levels had a positive impact; 2) human epidermal growth factor receptor 2 (HER2) positivity, baseline RBC, TSH, alkaline phosphatase, and alanine transferase (AST) levels had a negative impact. A slight increase in white blood cell (WBC) count (by 1.54, P = 0.02) and a drop in lymphocyte count (by 0.1907, P = 0.003) was significantly associated with disease progression. Conclusions: Baseline risk factors and monitoring blood counts can help predict outcomes in ICI-treated UGI tumors. We need larger studies to confirm this.
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页码：195 / 204
页数：10
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共 43 条
  • [1] Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, Yamaguchi K, Et al., Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer, Nature, 603, 7903, pp. 942-948, (2022)
  • [2] Janjigian YY, Kawazoe A, Bai Y, Xu J, Lonardi S, Metges JP, Yanez P, Et al., Pembrolizumab plus trastuzumab and chemotherapy for HER2-positive gastric or gastrooesophageal junction adenocarcinoma: interim analyses from the phase 3 KEYNOTE-811 randomised placebocontrolled trial, Lancet, 402, 10418, pp. 2197-2208, (2023)
  • [3] Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Et al., PD-1 blockade in tumors with mismatch-repair deficiency, N Engl J Med, 372, 26, pp. 2509-2520, (2015)
  • [4] Marabelle A, Le DT, Ascierto PA, Di Giacomo AM, De Jesus-Acosta A, Delord JP, Geva R, Et al., Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase II KEYNOTE-158 study, J Clin Oncol, 38, 1, pp. 1-10, (2020)
  • [5] Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, Doi T, Et al., Randomized phase III KEYNOTE-181 study of pembrolizumab versus chemotherapy in advanced esophageal cancer, J Clin Oncol, 38, 35, pp. 4138-4148, (2020)
  • [6] Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Et al., Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial, JAMA Oncol, 4, 5, (2018)
  • [7] Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Et al., Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial, Lancet, 390, 10111, pp. 2461-2471, (2017)
  • [8] Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, Ott PA, Et al., CheckMate-032 study: efficacy and safety of nivolumab and nivolumab plus ipilimumab in patients with metastatic esophagogastric cancer, J Clin Oncol, 36, 28, pp. 2836-2844, (2018)
  • [9] Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, 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, Lancet, 398, 10302, pp. 759-771, (2021)
  • [10] Doki Y, Ajani JA, Kato K, Xu J, Wyrwicz L, Motoyama S, Ogata T, Et al., Nivolumab Combination Therapy in Advanced Esophageal Squamous-Cell Carcinoma, N Engl J Med, 386, 5, pp. 449-462, (2022)
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