Dataset Information

A multicenter single-arm trial of sintilimab in combination with chemotherapy for neoadjuvant treatment of resectable esophageal cancer (SIN-ICE study).

ABSTRACT:

Background

Preoperative chemotherapy or chemoradiotherapy is the standard treatment for resectable esophageal cancer (EC); however, it is associated with increased postoperative complications and mortality. Recently, Immune Checkpoint inhibitors have been incorporated in the treatment of advanced EC. Its role in the preoperative setting has not been established yet. In this multicenter, single-arm study, we evaluated the efficacy and safety of neoadjuvant therapy with sintilimab in combination with chemotherapy in treating EC.

Methods

Patients received neoadjuvant therapy with 3 cycles of sintilimab 200 mg Q3W in combination with platinum-based chemotherapy. Surgery was performed within 4-6 weeks after neoadjuvant therapy. The primary endpoints of the trial were pathological complete response (pCR) and safety.

Results

A total of 23 patients (21 men and 2 women) were enrolled. Surgery was completed in 17 participants, with 16 achieving R0 resection and 1 had R1 resection, 5 participants refused surgery. One patient progressed prior to surgery. Twenty one patients (91%) had significant improvement in their dysphagia following treatment as assessed by Stooler's criteria. The majority of patients who underwent resection have a good pathological response and downstaging rate was 76.5% (13/17). A pCR was achieved in 6 cases (6/17, 35.3%) and major pathological response (MPR) in 9 cases (9/17, 52.9%). The main preoperative adverse events (AEs) were vomiting (13/23, 56.5%), leukopenia (12/23, 52.2%), neutropenia (9/23, 39.1%), and malaise (8/23, 34.8%). Immune-related AEs were mild and included hypothyroidism (2/23, 8.7%) and rash (4/23, 17.4%). The incidence of ≥ grade 3 treatment related AEs was 30.4% (7/23). There were no ≥ grade 4 AEs.

Conclusions

Sintilimab in combination with chemotherapy in the neoadjuvant treatment of EC is safe and lead to a high pCR. Therefore, further testing is warranted.

SUBMITTER: Duan H

PROVIDER: S-EPMC8667140 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

A multicenter single-arm trial of sintilimab in combination with chemotherapy for neoadjuvant treatment of resectable esophageal cancer (SIN-ICE study).

Duan Hongtao H Wang Tianhu T Luo Zhilin Z Wang Xiaoyuan X Liu Honggang H Tong Liping L Dong Xiaoping X Zhang Yong Y Valmasoni Michele M Kidane Biniam B Almhanna Khaldoun K Wiesel Ory O Pang Sainan S Ma Jianqun J Yan Xiaolong X

Annals of translational medicine 20211101 22

<h4>Background</h4>Preoperative chemotherapy or chemoradiotherapy is the standard treatment for resectable esophageal cancer (EC); however, it is associated with increased postoperative complications and mortality. Recently, Immune Checkpoint inhibitors have been incorporated in the treatment of advanced EC. Its role in the preoperative setting has not been established yet. In this multicenter, single-arm study, we evaluated the efficacy and safety of neoadjuvant therapy with sintilimab in combi ...[more]

PMID: 34988209

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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.

Project description:BackgroundThe study was conducted in order to investigate whether neoadjuvant immunotherapy combined with chemotherapy can bring survival benefits to patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) in the real world.MethodsWe retrospectively analysed patients with locally advanced resectable ESCC who underwent surgery at the Jining First People's Hospital from April 2020 to April 2022. Based on their medical history, the enrolled patients were divided into a neoadjuvant immunochemotherapy plus surgery group (nICT group) and a surgery-only group (S group). Primary endpoints were the two-year overall survival (OS) and disease-free survival (DFS) rates. Secondary endpoints were the safety and efficacy of neoadjuvant immunochemotherapy for patients with locally advanced esophageal cancer, and compared the surgery and postoperative outcomes between the two groups.ResultsA total of 47 patients in the nICT group and 73 patients in the S group were included for further analysis, the stage of the nICT group was more advanced than that of the S group. In the group nICT, 8 patients (17%) achieved the complete pathological response (pCR), 29 patients (61.7%) achieved major pathological response (MPR), including 6 patients (12.8%) with a primary tumor achieving pCR but had residual tumor cells in the lymph nodes (pT0N+), and the treatment-related AES was manageable. The surgery and postoperative outcomes were comparable in both groups. The two-year OS and DFS rates for the nICT group were 91.5% and 85.5% respectively, while those for the S group were 71.2% and 68.5%, and Kaplan-Meier survival analysis and log-rank test revealed significant differences in DFS and OS between the two groups. Patients who achieved MPR in the nICT group showed better DFS and OS, while the Three-cycle subgroup did not exhibit any survival benefit compared to the Two-cycle subgroup.ConclusionsNeoadjuvant sintilimab combined with chemotherapy has promising efficacy and safety in the treatment of locally advanced resectable ESCC. The treatment modality has the potential to become a standard therapy for locally advanced resectable ESCC.

Project description:BackgroundTo investigate the safety and feasibility of combining neoadjuvant sintilimab (Innovent Biologics, Suzhou, China) and chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC).MethodsThe study was an investigator-initiated, open-label, non-randomized, single-arm, single-center phase 2 trial. Patients aged between 18 to 75 years with locally advanced ESCC were eligible for neoadjuvant immunochemotherapy (nICT). The nICT included cisplatin (60 mg/m2) on day 1, albumin-bound paclitaxel (125 mg/m2) on days 1 and 8, and sintilimab (200 mg) on day 1 of each 21-day cycle. Clinical evaluation was conducted after 2 cycles of nICT. Within 4-6 weeks after nICT, patients underwent esophagectomy. The primary end points were pathological complete response (pCR) and adverse events (AEs). Secondary endpoints included major pathological response (MPR), R0 resection rate, interval to surgery, and 30-day complications. This trial was registered at chictr.org.cn, ChiCTR2100045659.ResultsFrom July 2020 to June 2021, 30 patients were enrolled. All patients successfully completed 2 cycles of nICT. AEs were common during nICT, and the most common AE was anorexia (20/30, 67%). However, only one patient with grade 3 ESCC had increased transaminase. According to radiologic evaluations, the objective response rate (ORR) was 67% (20/30) and the disease control rate 97% (29/30). Twenty-three patients underwent McKeown minimally invasive esophagectomy (MIE). The pCR rate of the primary tumor was 21.7%, and the MPR rate of the primary tumor was 52.2%. The median interval to surgery was 40 days, and no patients delayed surgery due to AEs. Pneumonia was the most common major 30-day postoperative complication (9/23, 39%). Anastomotic leakage (AL) occurred in two patients during the hospital stay, and one patient was readmitted due to AL. There was no treatment- or surgery-related deaths.ConclusionsNeoadjuvant sintilimab plus chemotherapy for locally advanced ESCC appears to be safe and feasible with limited AEs, high R0 resection rate, promising pCR rate, and manageable postoperative complications. Long-term follow-up is required. A multicenter, randomized, phase III clinical trial assessing the efficacy and safety of sintilimab versus placebo in combination with chemotherapy in locally advanced ESCC is warranted to confirm these results.

Project description:BackgroundConcurrent chemoradiotherapy is the standard nonoperative treatment for locally advanced esophageal squamous cell carcinoma. However, local recurrence is still the main failure pattern, accounting for more than half of all treatment failures, indicating that the sensitivity of radiotherapy still needs to be improved. This trial aimed at demonstrating whether PD-1 inhibitors followed by chemoradiotherapy could promote esophageal tumor vascular normalization, alleviate hypoxia, and thus enhance radiosensitivity and improve local control.MethodsWe did a multicenter, single-arm, phase 2 trial in China. Patients with locally advanced esophageal cancer were enrolled in this study. In induction phase, patients received two cycles of sintilimab, paclitaxel and carboplatin once per 21 days. In concurrent phase, patients were treated with five cycles of carboplatin and paclitaxel once per week concurrent with radiotherapy of 50.4Gy delivered in 28 fractions. The primary endpoint was 2-year local control rate. Hypoxia and vessel normalization was assessed before and after induction phase using immunofluorescence and perfusion CT. This trial is registered with ClinicalTrials.gov (NCT03985046).FindingsSeventy-five patients with esophageal cancer were enrolled in this study between October 2019 and April 2021. The median follow-up of surviving patients was 33.6 months (IQR 29.3-35.7). The 2-year local control rate was 81.7% (95% confidence interval, 72.7%-90.7%), which was much higher than that in concurrent chemoradiation only (71.3%) in previous studies. Vascular normalization and hypoxia alleviation were observed in both biopsy specimens and perfusion CT.InterpretationThe addition of induction immunotherapy to standard concurrent chemoradiotherapy could improve radiosensitivity for locally advanced esophageal cancer as non-surgical treatment. New treatment combination led to higher local control rate through promoting vascular normalization and alleviating hypoxia. Our findings suggest that induction immunotherapy followed by concurrent chemoradiotherapy could be a potential option in future treatment.FundingNational Natural Science Foundation of China and Shanghai Rising-Star Program.

Project description:Background Neoadjuvant 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 methods PubMed, 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. Results Twenty-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. Conclusion Both 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.

Dataset Information

A multicenter single-arm trial of sintilimab in combination with chemotherapy for neoadjuvant treatment of resectable esophageal cancer (SIN-ICE study).

Background

Methods

Results

Conclusions

Publications

A multicenter single-arm trial of sintilimab in combination with chemotherapy for neoadjuvant treatment of resectable esophageal cancer (SIN-ICE study).

Similar Datasets

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