Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

He, Wenwu; Leng, Xuefeng; Mao, Tianqin; Luo, Xi; Zhou, Lingxiao; Yan, Jiaxin; Lin, Peng; Fang, Qiang; Liu, Guangyuan; Xing, Wei; Wang, Kangning; Wang, Chenghao; Zhang, Sha; Zhang, Xudong; Shen, Xudong; Huang, Depei; Yi, Huan; Bei, Ting; She, Xueke; Xiao, Wei; Han, Yongtao

doi:10.1093/oncolo/oyab011

Cited by 55 publications

(91 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It had been reported that TPS had a better prediction performance than CPS in EC ( 21 ). Moreover, PD-L1 expression can be upregulated by CT/CRT in patients with EC ( 38 , 48 , 49 ). In a phase 2 trial of EC ( 38 ), there were 5 patients (29%) whose CPS changed from 0 before nICT to ≥ 1 after nICT.…”

Section: Discussionmentioning

confidence: 99%

“…The selection process and reasons for study exclusion are shown in Figure 1. Among the 27 studies, 8 trials with 221 patients examined nICRT (14-21), 19 trials with 588 patients examined nICT (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40). Except one twoarms trial (33), all included studies were single-arm trials.…”

Section: Eligible Studiesmentioning

confidence: 99%

See 1 more Smart Citation

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis

Wang

Liu

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

BackgroundNeoadjuvant immune checkpoint inhibitor in combination with chemotherapy (nICT) or chemoradiotherapy (nICRT) has been tested in resectable esophageal cancer. Nevertheless, efficacy and safety for this new strategy have not been clearly demonstrated.Patients and methodsPubMed, Embase, Cochrane Library, Web of Science, and scientific meetings were searched for eligible trials until June 30, 2022. The primary outcome of interest was pathological complete response (pCR). The random-effect model was used for statistical analysis.ResultsTwenty-seven trials with 809 patients were identified. The estimated rates of pCR for nICRT and nICT were comparable (32.7%, 95% CI: 20.3%-45.1% vs 26.3%, 95% CI: 19.8%-32.8%; P = 0.37). As for safety, surgical resection rate, R0 resection rate, surgical delay rate, and surgical mortality rate were similar between nICRT and nICT, while more grade ≥3 treatment-related adverse events were observed for nICRT (52.6%, 95% CI: 30.7%-74.5% vs 19.9%, 95% CI: 8.8%-31.0%; P = 0.01). In subgroup analysis, nICRT achieved higher pCR rate compared to nICT (56.2%, 95% CI: 41.0%-71.3% vs 27.2%, 95% CI: 20.2%-34.1%; P < 0.001) for squamous cell carcinoma (SCC) but adenocarcinoma. In patients receiving nICT, PD-L1 expression CPS ≥1 showed higher pCR rate compared to CPS <1 (51.3%, 95% CI: 41.4%-61.2% vs 26.6%, 95% CI: 8.6%-44.5%; P = 0.02); regimen of paclitaxel plus carboplatin/cisplatin (PC/TP) and 3-4 cycles of nICT did not lead to an significantly improved pCR rate compared to other chemotherapy regimens and 2 cycles of nICT, respectively, despite without increased toxicity.ConclusionBoth nICT and nICRT achieved promising pCR rates with acceptable tolerability, and nICRT was likely to have more antitumor efficacy compared to nICT for patients with SCC. PD-L1 status seemed to be predictive of pCR in patients receiving nICT; pCR rate did not appear to be greatly affected by CT regimen and increasing cycles of nICT.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Eligible Studiesmentioning

confidence: 99%

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis

Wang

Liu

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Of the 21 studies included, there were 20 single-arm open-label cohort studies ( 15 , 19 – 37 ) and there was one two-arm open-label randomized controlled trial (RCT) ( 38 ). Of the 21 studies included, three are still ongoing ( 26 , 29 , 30 ) and 18 ( 15 , 19 – 25 , 27 , 28 , 31 – 38 ) have been completed. The main neoadjuvant immunotherapy drugs include pembrolizumab, sintilimab, and camrelizumab, amongst others.…”

Section: Resultsmentioning

confidence: 99%

“…Twelve of the 21 studies achieved 100% R0 resection, with an overall mean R0 resection rate of 97.5%. The remaining nine studies ( 15 , 19 , 23 – 25 , 27 , 32 , 36 , 37 ) had individual ORs as well as combined ORs <1 (OR=0.95,95% CI: 0.90–1.00, p <0.001; Figure 5 ). Heterogeneity ( p <0.001, I 2 = 94%) was significant, so a random-effects model was used.…”

Section: Resultsmentioning

confidence: 99%

“…To understand the possible correlation between the type of ICI and the outcome of neoadjuvant immunotherapy in combination with chemotherapy, we performed subgroup analysis. The 21 selected studies included two studies in which patients were treated with pembrolizumab ( 36 , 38 ), four studies in which patients were treated with sintilimab ( 27 , 32 , 33 , 37 ), four studies in which patients were treated with toripalimab ( 20 , 25 , 26 , 34 ), and nine studies in which patients were treated with Carlizumab ( 19 , 21 – 23 , 28 – 31 , 35 ).The potential correlation between ICI type and the efficacy and safety of neoadjuvant immunotherapy in combination with chemotherapy has not seen significant findings, implying that ICI type does not currently predominate in neoadjuvant immunotherapy ( Figure 12 ).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis

et al. 2022

View full text Add to dashboard Cite

ObjectiveThe progress of neoadjuvant therapy for resectable locally advanced esophageal cancer has been stagnant. There has been much progress in immunotherapy for advanced esophageal cancer, but the efficacy and safety of neoadjuvant immunotherapy for resectable locally advanced esophageal cancer have not yet been definitively demonstrated.MethodsOriginal articles describing the safety and efficacy of neoadjuvant immunotherapy in resectable locally advanced esophagus published until July 2022 were retrieved from PubMed, Embase, and the Cochrane Library. The ratio (OR) and 95% confidence interval (CI) were calculated to conduct heterogeneity and subgroup analysis.ResultsIn total, 759 patients from 21 studies were enrolled. The effectiveness of neoadjuvant immunotherapy in combination with chemotherapy was evaluated using the major pathologic response (MPR) and pathologic complete response (PCR). In the enrolled patients, 677 were treated surgically and 664 achieved R0 resection. Major pathological remission was achieved in 52.0% (95% CI: 0.44–0.57) of patients on neoadjuvant immunotherapy combined with chemotherapy and complete pathological remission in 29.5% (95% CI: 0.25–0.32) of patients. The safety was primarily assessed by the incidence of treatment-related adverse events (TRAEs) and surgical resection rates. The incidence of TRAEs and the surgical resection rate combined ORs were 0.15 (95% CI: 0.09–0.22) and 0.86 (95% CI: 0.83–0.89), respectively.ConclusionNeoadjuvant immunotherapy combined with chemotherapy in locally advanced resectable esophageal cancer is effective and safe.

show abstract

Evaluation of Clinical and Safety Outcomes of Neoadjuvant Immunotherapy Combined With Chemotherapy for Patients With Resectable Esophageal Cancer

Huo

et al. 2022

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceA considerable number of clinical trials of neoadjuvant immunotherapy for patients with resectable esophageal cancer are emerging. However, systematic evaluations of these studies are lacking.ObjectiveTo provide state-of-the-art evidence and normative theoretical support for neoadjuvant immunotherapy for locally advanced resectable esophageal cancer.Data SourcesPubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched for relevant original articles and conference proceedings that were published in English through April 1, 2022.Study SelectionPublished phase 2 or 3 clinical trials that included patients with resectable stage I to IV esophageal cancer who received immune checkpoint inhibitors (ICIs) before surgery as monotherapy or in combination with other therapies.Data Extraction and SynthesisThe Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Meta-analysis of Observational Studies in Epidemiology guidelines for meta-analysis were followed to extract data. A random-effects model was adopted if the heterogeneity was significant (I2 statistic &gt;50%); otherwise, the common-effects model was used. Data analyses were conducted from April 2 to 8, 2022.Main Outcomes and MeasuresPathological complete response (pCR) rate and major pathological response (MPR) rate were considered to be the primary outcomes calculated for the clinical outcomes of neoadjuvant immunotherapy. Incidence of treatment-related severe adverse events was set as the major measure for the safety outcome. The rate of R0 surgical resection was summarized. Subgroup analyses were conducted according to histologic subtype and ICI types.ResultsA total of 27 clinical trials with 815 patients were included. Pooled rates were 31.4% (95% CI, 27.6%-35.3%) for pCR and 48.9% (95% CI, 42.0-55.9%) for MCR in patients with esophageal cancer. In terms of safety, the pooled incidence of treatment-related severe adverse events was 26.9% (95% CI, 16.7%-38.3%). Most patients achieved R0 surgical resection (98.6%; 95% CI, 97.1%-99.6%). Regarding histologic subtypes, the pooled pCR rates were 32.4% (95% CI, 28.2%-36.8%) in esophageal squamous cell carcinoma and 25.2% (95% CI, 16.3%-35.1%) in esophageal adenocarcinoma. The pooled MPR rate was 49.4% (95% CI, 42.1%-56.7%) in esophageal squamous cell carcinoma.Conclusions and RelevanceThis study found that neoadjuvant immunotherapy with chemotherapy had promising clinical and safety outcomes for patients with resectable esophageal cancer. Randomized clinical trials with long-term follow-up are warranted to validate the findings and benefits of ICIs.

show abstract

Toripalimab Plus Paclitaxel and Carboplatin as Neoadjuvant Therapy in Locally Advanced Resectable Esophageal Squamous Cell Carcinoma

Cited by 55 publications

References 53 publications

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis

Neoadjuvant immune checkpoint inhibitor in combination with chemotherapy or chemoradiotherapy in resectable esophageal cancer: A systematic review and meta-analysis

Efficacy and safety of neoadjuvant immunotherapy combined with chemotherapy in locally advanced esophageal cancer: A meta-analysis

Evaluation of Clinical and Safety Outcomes of Neoadjuvant Immunotherapy Combined With Chemotherapy for Patients With Resectable Esophageal Cancer

Contact Info

Product

Resources

About