Dataset Information

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

ABSTRACT:

Introduction

Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data.

Methods

In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in each 3-week cycle for 2 cycles, followed by esophagectomy planned 4-6 weeks after preoperative therapy. The primary endpoints were safety, feasibility, and the major pathological response (MPR) rate; the secondary endpoints were the pathological complete response (pCR) rate, disease-free survival (DFS), and overall survival (OS). Association between molecular signatures/tumor immune microenvironment and treatment response was also explored.

Results

Twenty resectable ESCC patients were enrolled. Treatment-related adverse events (AEs) occurred in all patients (100%), and 4 patients (22.2%) experienced grade 3 or higher treatment-related AEs. Sixteen patients underwent surgery without treatment-related surgical delay, and the R0 resection rate was 87.5% (14/16). Among the 16 patients, the MPR rate was 43.8% (7/16) and the pCR rate was 18.8% (3/16). The abundance of CD8+ T cells in surgical specimens increased (P = .0093), accompanied by a decreased proportion of M2-type tumor-associated macrophages (P = .036) in responders upon neoadjuvant therapy. Responders were associated with higher baseline gene expression levels of CXCL5 (P = .03) and lower baseline levels of CCL19 (P = .017) and UMODL1 (P = .03).

Conclusions

The combination of toripalimab plus paclitaxel and carboplatin is safe, feasible, and effective in locally advanced resectable ESCC, indicating its potential as a neoadjuvant treatment for ESCC.

Clinical trial registration

NCT04177797.

SUBMITTER: He W

PROVIDER: S-EPMC8842349 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

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

He Wenwu W Leng Xuefeng X Mao Tianqin T Luo Xi X Zhou Lingxiao L Yan Jiaxin J Peng Lin L Fang Qiang Q Liu Guangyuan G Wei Xing X Wang Kangning K Wang Chenghao C Zhang Sha S Zhang Xudong X Shen Xudong X Huang Depei D Yi Huan H Bei Ting T She Xueke X Xiao Wenguang W Han Yongtao Y

The oncologist 20220201 1

<h4>Introduction</h4>Immune checkpoint inhibitors (ICIs) are effective in the treatment of advanced esophageal squamous cell carcinoma (ESCC); however, their efficacy in locally advanced resectable ESCC and the potential predictive biomarkers have limited data.<h4>Methods</h4>In this study, locally advanced resectable ESCC patients were enrolled and received neoadjuvant toripalimab (240 mg, day 1) plus paclitaxel (135 mg/m2, day 1) and carboplatin (area under the curve 5 mg/mL per min, day 1) in ...[more]

PMID: 35305102

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Project description:BackgroundProgrammed death 1 (PD-1) inhibitor demonstrated durable antitumor activity in advanced esophageal squamous cell carcinoma (ESCC), but the clinical benefit of perioperative immunotherapy in ESCC remains unclear. This study evaluated the efficacy and safety of neoadjuvant chemoradiotherapy (nCRT) combined with the PD-1 inhibitor toripalimab in patients with resectable ESCC.MethodsFrom July 2020 to July 2022, 21 patients with histopathologically confirmed thoracic ESCC and clinical staged as cT1-4aN1-2M0/cT3-4aN0M0 were enrolled. Eligible patients received radiotherapy (23 fractions of 1.8 Gy, 5 fractions a week) with concurrent chemotherapy of paclitaxel/cisplatin (paclitaxel 45 mg/m2 and cisplatin 25 mg/m2) on days 1, 8, 15, 22, 29 and two cycles of toripalimab 240 mg every 3 weeks after nCRT for neoadjuvant therapy before surgery, four cycles of toripalimab 240 mg every 3 weeks for adjuvant therapy after surgery. The primary endpoint was the major pathological response (MPR) rate. The secondary endpoints were safety and survival outcomes.ResultsA total of 21 patients were included, of whom 20 patients underwent surgery, 1 patient refused surgery and another patient was confirmed adenocarcinoma after surgery. The MPR and pathological complete response (pCR) rates were 78.9% (15/19) and 47.4% (9/19) for surgery ESCC patients. 21 patients (100.0%) had any-grade treatment-related adverse events, with the most common being lymphopenia (100.0%), leukopenia (85.7%), neutropenia (52.4%). 14 patients (66.7%) had adverse events of grade 3 with the most common being lymphopenia (66.7%). The maximum standardized uptake value and total lesion glycolysis of positron emission tomography/CT after neoadjuvant therapy well predicted the pathological response. The peripheral CD4+%, CD3+HLA-DR+/CD3+%, CD8+HLA-DR+/CD8+%, and IL-6 were significant differences between pCR and non-pCR groups at different times during neoadjuvant therapy. Three patients had tumor relapse and patients with MPR have longer disease-free survival than non-MPR patients.ConclusionsnCRT combined with perioperative toripalimab is effective and safe for locally advanced resectable ESCC. Long-term survival outcomes remain to be determined.Trial registration numberNCT04437212.

Project description:BackgroundAdding immune checkpoint inhibitors (ICIs) to the chemotherapy has shown significant clinical benefits in neoadjuvant treatment of locally advanced esophageal squamous cell carcinoma (ESCC). Sintilimab is one such ICI used for treatment. Herein, we designed a trial to evaluate the safety and efficacy of sintilimab combined with paclitaxel and platinum for locally advanced resectable ESCC.MethodsPatients with locally advanced resectable (stage II-III) ESCC were enrolled and received at least two cycles of neoadjuvant therapy with sintilimab (200 mg on day 1) plus platinum-based chemotherapy in each 3-week cycle followed by esophagectomy. The primary endpoint of the trial was the pathological complete response (pCR) rate. The secondary endpoints were the major pathological response (MPR) rate, the objective response rate (ORR), the treatment-related adverse events (TRAEs), the immune-related adverse events (irAEs) and quality of life (QOL). Besides, relapse-free survival (RFS), overall survival (OS) were exploratory endpoints. Forty-three cases were needed to be enrolled in this trial. It was assumed the regimen of the neoadjuvant sintilimab plus chemotherapy would achieve a pCR rate of 30.5%.ResultsBetween March 2021 and January 2023, a total of 43 patients (41 men and 2 women) were enrolled, including 11 cases (25.6%) of clinical stage II and 32 cases (74.4%) of clinical stage III at baseline. All the 43 patients completed two cycles of neoadjuvant therapy, and 32 patients received McKeown radical resection for esophageal cancer. The pCR rate was 28.1% (9/32), which was below the 30.5% reference cutoff value, and the MPR rate was 37.5% (12/32). According to RECIST 1.1, four patients (4/43, 9.3%) had a complete response (CR), 21 patients (21/43, 48.8%) had a partial response (PR), ORR was 58.1% (25/43). The incidence of ≥ grade 3 TRAEs was 23.3% (10/43) and there were no ≥ grade 4 TRAEs.ConclusionsSintilimab plus platinum-based chemotherapy as neoadjuvant therapy is safe, feasible and effective in locally advanced resectable ESCC, suggesting a supportive rationale for its further evaluation in randomized clinical trials.Trial registrationChinese Clinical Trial Registry identifier: ChiCTR2200056558.

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Dataset Information

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

Introduction

Methods

Results

Conclusions

Clinical trial registration

Publications

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

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