Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer

Li, Song; Yu, Wenbin; Xie, Fei; Luo, Haitao; Liu, Zhimin; Lv, Weiwei; Shi, Duan-Bo; Yu, Dexin; Gao, Peng; Chen, Cheng; Wei, Meng; Zhou, Wenhao; Wang, Hua; Zhao, Zhikun; Dai, Xin; Xu, Qian; Zhang, Xue; Hao, Miao; Huang, Kai; Wang, Jian; Li, Jisheng; Sheng, Lei; Liu, Lian

doi:10.1038/s41467-022-35431-x

Cited by 102 publications

(68 citation statements)

References 85 publications

(97 reference statements)

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“…1). We defined the ORR as pCR (no residual tumor cells in the resected specimens and all resected lymph nodes) + major pathological response (≤ 10% viable tumor cells in the resected primary tumor and all resected lymph nodes) + partial pathological response (≤ 50% viable tumor cells in the resected primary tumor and all resected lymph nodes) 15,16 .…”

Section: Methodsmentioning

confidence: 99%

Factors affecting the ORR after neoadjuvant therapy of TP regimen combined with PD-1 inhibitors for esophageal cancer

Yuan

et al. 2023

Sci Rep

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The aim of this study is to evaluate the factors affecting the objective response rate (ORR) after neoadjuvant therapy of taxol plus platinum (TP) regimen combined with programmed cell death protein-1 (PD-1) inhibitors for esophageal cancer, and establish a predictive model for forecasting ORR. According to the inclusion and exclusion criteria, consecutive esophageal cancer patients who were treated in the First Affiliated Hospital of Xi’an Jiaotong University from January 2020 to February 2022 were enrolled in this study as a training cohort, while patients who were treated in the Shaanxi Provincial Cancer Hospital Affiliated to Medical College of Xi’an Jiaotong University from January 2020 to December 2021 were enrolled as a validation cohort. All patients were treated with resectable locally advanced esophageal cancer and received neoadjuvant chemotherapy combined with immunotherapy. The ORR was defined as the sum of complete pathological response, major pathological response and partial pathological response. Logistic regression analysis was performed to determine the factors that might be related to the ORR of the patients after neoadjuvant therapy. The nomogram based on the result of regression analysis was established and verified to predict the ORR. In this study, 42 patients were included as training cohort and 53 patients were included as validation cohort. Chi-square analysis showed that neutrophil, platelet, platelet-to-lymphocytes ratio (PLR), systemic immune-inflammation index (SII), D-dimer and carcinoembryonic antigen (CEA) between ORR group and non-ORR group were significantly different. Logistic regression analysis showed that aspartate aminotransferase (AST), D-dimer and CEA were independent predictors of ORR after neoadjuvant immunotherapy. Finally, a nomogram was established based on AST, D-dimer and CEA. Internal validation and external validation revealed that the nomogram had a good ability to predict ORR after neoadjuvant immunotherapy. In conclusion, AST, D-dimer and CEA were the independent predictors of ORR after neoadjuvant immunotherapy. The nomogram based on these three indicators showed a good predictive ability.

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Section: Methodsmentioning

confidence: 99%

Factors affecting the ORR after neoadjuvant therapy of TP regimen combined with PD-1 inhibitors for esophageal cancer

Yuan

et al. 2023

Sci Rep

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“…29 Several previous studies have shown that LAGC/GEJC patients with positive PD-L1 have a higher chance of achieving pCR, but no definite conclusion can be drawn because of lack of randomized phase III studies, and potential bias may occur due to our small sample size. 24,30,31 There are several limitations exist in our study: Firstly, our study is a single-arm study without a control group; secondly, the patients in our study were recruited from a single-center and the number was limited, which may cause potential bias; thirdly, the follow-up of EFS and OS is still ongoing and the data are immature at present, further results are warranted to analyze survival benefits.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of camrelizumab combined with oxaliplatin and S‐1 as neoadjuvant treatment in locally advanced gastric or gastroesophageal junction cancer: A phase II, single‐arm study

Zhong,

Lin,

et al. 2024

Cancer Medicine

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PurposeIn the present study, we aimed to evaluate the efficacy and safety of camrelizumab combined with oxaliplatin plus S‐1 in patients with resectable gastric or gastroesophageal junction cancer.MethodsIn this single‐arm, phase II clinical trial, patients with locally advanced gastric or gastroesophageal junction adenocarcinoma were enrolled to receive three cycles of neoadjuvant camrelizumab and oxaliplatin plus S‐1 every 3 weeks, followed by surgical resection and adjuvant therapy with the same regimen. The primary endpoint was pathological complete response (pCR) (ypT0) rate and secondary endpoints were R0 resection rate, total pCR (tpCR, ypT0N0) rate, major pathological response (MPR) rate, downstaging, objective response rate (ORR), disease control rate (DCR), event‐free survival (EFS), overall survival (OS), and safety.ResultsBetween September, 2020 and January, 2022, a total of 29 patients were enrolled in the present study, all of whom completed neoadjuvant therapy and underwent surgery. Three (10.3%) (95% CI: 2.2–27.4) patients achieved pCR as well as tpCR, 20 (69.0%) patients had MPR and 28 (96.6%) patients achieved R0 resection. Treatment‐emergent adverse events (AEs) of any grade were observed in 24 (82.8%) patients. Immune‐related adverse events of any grade were reported in 13 (44.8%) patients, whereas no grade 3 or higher adverse events occurred.ConclusionThe neoadjuvant therapy with camrelizumab in combination with oxaliplatin and S‐1 showed a modest pCR rate, and favorable MPR rate and safety profile in patients with gastric or gastroesophageal junction cancer.

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“…In the EPOC1706 study, combination of pembrolizumab and lenvatinib resulted in a 69% ORR as first-or second-line treatment in 29 advanced or metastatic G/GEJ adenocarcinoma cases (13). Recently, there were several preliminary explorations about the application of anti-PD-1 agent plus anti-angiogenic drug and chemotherapy in second-line (14) and pre-operative (15) therapy of advanced GC. A phase 2, single-arm, prospective study assessed the efficacy and safety of the combination therapy of camrelizumab, apatinib, and S-1 in patients with G/GEJ adenocarcinoma as second-line treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Complete and major pathological response (pCR and MPR) rates were 15.8% and 26.3%, respectively. Grade 3 or higher adverse events occurred in 2 out of 25 patients (15). Although these studies have explored the application of immunotherapy plus antiangiogenic drugs and chemotherapy in treating advanced or metastatic GC, and indicated its efficacy and safety in…”

Section: Introductionmentioning

confidence: 99%

Anti-PD-1 plus anti-angiogenesis combined with chemotherapy in patients with HER2-negative advanced or metastatic gastric cancer: a multi-institutional retrospective study

Xu¹,

Wang²,

Bao³

et al. 2023

J Gastrointest Oncol

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Background: Immunotherapy plus chemotherapy have been confirmed to be effective in treating advanced or metastatic gastric cancer (GC). Anti-programmed death-1 (PD-1) plus antiangiogenic agents have shown promising activity and tolerant toxicity in subsequent therapy of late-stage gastric cancer. The aim of this study was to assess the efficacy and safety of anti-PD-1 plus anti-angiogenic agents and chemotherapy in advanced or metastatic GC and to explore the potential biomarkers associated with response.Methods: We retrospectively reviewed thirty human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic GC patients who received PD-1 plus anti-angiogenic drugs and chemotherapy.Conversion therapy was defined when the patients could undergo resection post combination therapy.Clinical data were retrieved from medical records. We conducted exploratory biomarker analysis of baseline gene mutations and tumor mutation burden (TMB) using the next-generation sequencing (NGS), PD-L1 by immunohistochemistry (IHC), and the tumor immune microenvironment (TIME) by multiplex immunofluorescence.Results: A total of 30 patients received anti-PD-1plus anti-angiogenic drugs and chemotherapy during the study period. The objective response rate (ORR) was 76.7% [95% confidence interval (CI): 57.7-90.1%] and disease control rate (DCR) was 86.7% (95% CI: 69.3-96.2%). A total of 11 patients (36.7%) achieved conversion therapy and underwent surgery. The R0 resection rate was 90.9%. Of the 11 patients, 9 (81.8%) responded to the treatment, 1 with a pathological complete response (pCR) and 8 with a major pathological response (MPR). No adverse events of grade 3 or higher occurred. Neither PD-L1 expression nor TMB was significantly correlated with treatment response. Analysis of TIME revealed that the fraction of CD8 + T cell in the invasive margin was higher in responders than non-responders before treatment. TAM2 in the tumor center and CD8 + T cell in the invasive margin was significantly increased after combination therapy, which suggested that combination therapy promoted infiltration of CD8 + T cells, thereby exerting an antitumor effect.Conclusions: Immunotherapy plus anti-angiogenic drugs and chemotherapy is a promising treatment strategy for advanced or metastatic GC patients. Tumor infiltration CD8 + T cells may serve as potential predictive biomarker.

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Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer

Cited by 102 publications

References 85 publications

Factors affecting the ORR after neoadjuvant therapy of TP regimen combined with PD-1 inhibitors for esophageal cancer

Factors affecting the ORR after neoadjuvant therapy of TP regimen combined with PD-1 inhibitors for esophageal cancer

Efficacy and safety of camrelizumab combined with oxaliplatin and S‐1 as neoadjuvant treatment in locally advanced gastric or gastroesophageal junction cancer: A phase II, single‐arm study

Anti-PD-1 plus anti-angiogenesis combined with chemotherapy in patients with HER2-negative advanced or metastatic gastric cancer: a multi-institutional retrospective study

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