Dataset Information

Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2).

ABSTRACT: This randomized, open-label, multi-center phase 2 study (NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemotherapy in patients with esophageal squamous cell carcinoma after first-line chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with efficacy. The median OS in the sintilimab group was significantly improved compared with the chemotherapy group (median OS 7.2 vs.6.2 months; P = 0.032; HR = 0.70; 95% CI, 0.50-0.97). Incidence of treatment-related adverse events of grade 3-5 was lower with sintilimab than with chemotherapy (20.2 vs. 39.1%). Patients with high T-cell receptor (TCR) clonality and low molecular tumor burden index (mTBI) showed the longest median OS (15.0 months). Patients with NLR < 3 at 6 weeks post-treatment had a significantly prolonged median OS (16.6 months) compared with NLR ≥ 3. The results demonstrate a significant improvement in OS of sintilimab compared to chemotherapy as second-line treatment for advanced or metastatic ESCC.

SUBMITTER: Xu J

PROVIDER: S-EPMC8844279 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2).

Xu Jianming J Li Yi Y Fan Qingxia Q Shu Yongqian Y Yang Lei L Cui Tongjian T Gu Kangsheng K Tao Min M Wang Xiuwen X Cui Chengxu C Xu Nong N Xiao Juxiang J Gao Quanli Q Liu Yunpeng Y Zhang Tao T Bai Yuxian Y Li Wei W Zhang Yiping Y Dai Guanghai G Ma Dong D Zhang Jingdong J Bai Chunmei C Huang Yunchao Y Liao Wangjun W Wu Lin L Chen Xi X Yang Yan Y Wang Junye J Ji Shoujian S Zhou Hui H Wang Yan Y Ma Zhuo Z Wang Yanqi Y Peng Bo B Sun Jiya J Mancao Christoph C

Nature communications 20220214 1

This randomized, open-label, multi-center phase 2 study (NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemotherapy in patients with esophageal squamous cell carcinoma after first-line chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with efficacy. The median OS in the sintilimab group was significantly improved compared with the chemotherapy group (median OS 7.2 vs.6.2 months; P = 0.032; HR = 0.70; 95% CI, 0. ...[more]

PMID: 35165274

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Project description:BackgroundTreatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer (sqNSCLC) after failure of first-line chemotherapy are limited. This study (ORIENT-3) aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.MethodsORIENT-3 was an open-label, multicenter, randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy. Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m2 of docetaxel intravenously every 3 weeks, stratified by the Eastern Cooperative Oncology Group performance status. The primary endpoint was overall survival (OS) in the full analysis set (FAS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR) and safety.ResultsBetween August 25, 2017, and November 7, 2018, 290 patients were randomized. For FAS, 10 patients from the docetaxel arm were excluded. The median OS was 11.79 (n = 145; 95% confidence interval [CI], 10.28-15.57) months with sintilimab versus 8.25 (n = 135; 95% CI, 6.47-9.82) months with docetaxel (hazard ratio [HR]: 0.74; 95% CI, 0.56-0.96; P = 0.025). Sintilimab treatment significantly prolonged PFS (median 4.30 vs. 2.79 months; HR: 0.52; 95% CI, 0.39-0.68; P < 0.001) and showed higher ORR (25.50% vs. 2.20%, P < 0.001) and DCR (65.50% vs. 37.80%, P < 0.001) than the docetaxel arm. The median DoR was 12.45 (95% CI, 4.86-25.33) months in the sintilimab arm and 4.14 (95% CI, 1.41-7.23) months in the docetaxel arm (P = 0.045). Treatment-related adverse events of grade ≥ 3 were reported in 26 (18.1%) patients in the sintilimab arm and 47 (36.2%) patients in the docetaxel arm. Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors, including OVOL2 (HR: 0.35; P < 0.001) and CTCF (HR: 3.50; P < 0.001)，for sintilimab treatment.ConclusionsCompared with docetaxel, sintilimab significantly improved the OS, PFS, and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.

Project description:ObjectiveTo evaluate sintilimab versus placebo in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil) as first line treatment of unresectable locally advanced, recurrent, or metastatic oesophageal squamous cell carcinoma.DesignMulticentre, randomised, double blind, phase 3 trial.Setting66 sites in China and 13 sites outside of China between 14 December 2018 and 9 April 2021.Participants659 adults (aged ≥18 years) with advanced or metastatic oesophageal squamous cell carcinoma who had not received systemic treatment.InterventionParticipants were randomised 1:1 to receive sintilimab or placebo (3 mg/kg in patients weighing <60 kg or 200 mg in patients weighing ≥60 kg) in combination with cisplatin 75 mg/m2 plus paclitaxel 175 mg/m2 every three weeks. The trial was amended to allow investigators to choose the chemotherapy regimen: cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil (800 mg/m2 continuous infusion on days 1-5).Main outcome measuresOverall survival in all patients and in patients with combined positive scores of ≥10 for expression of programmed cell death ligand 1.Results659 patients were randomly assigned to sintilimab (n=327) or placebo (n=332) with chemotherapy. 616 of 659 patients (93%) received sintilimab or placebo in combination with cisplatin plus paclitaxel and 43 of 659 patients (7%) received sintilimab or placebo in combination with cisplatin plus 5-fluorouracil. At the interim analysis, sintilimab with chemotherapy showed better overall survival compared with placebo and chemotherapy in all patients (median 16.7 v 12.5 months, hazard ratio 0.63, 95% confidence interval 0.51 to 0.78, P<0.001) and in patients with combined positive scores of ≥10 (17.2 v 13.6 months, 0.64, 0.48 to 0.85, P=0.002). Sintilimab and chemotherapy significantly improved progression free survival compared with placebo and chemotherapy in all patients (7.2 v 5.7 months, 0.56, 0.46 to 0.68, P<0.001) and in patients with combined positive scores of ≥10 (8.3 v 6.4 months, 0.58, 0.45 to 0.75, P<0.001). Adverse events related to treatment occurred in 321 of 327 patients (98%) in the sintilimab-chemotherapy group versus 326 of 332 (98%) patients in the placebo-chemotherapy group. Rates of adverse events related to treatment, grade ≥3, were 60% (196/327) and 55% (181/332) in the sintilimab-chemotherapy and placebo-chemotherapy groups, respectively.ConclusionsCompared with placebo, sintilimab in combination with cisplatin plus paclitaxel showed significant benefits in overall survival and progression free survival as first line treatment in patients with advanced or metastatic oesophageal squamous cell carcinoma. Similar benefits of sintilimab with cisplatin plus 5-fluorouracil seem promising.Trial registrationClinicalTrials.gov NCT03748134.

Project description:BackgroundFor advanced gastric cancer (GC) patients who fail first-line treatment, chemotherapy alone is of limited benefit. Ramucirumab combined with paclitaxel and apatinib combined with docetaxel provided clinical benefit in previous studies, but the feasibility of apatinib combined with other chemotherapy agents remains unknown. The aim of the present study was to evaluate the efficacy and safety of apatinib combined with chemotherapy as a second-line treatment for advanced GC.MethodsPatients aged 18-75 years with histologically or cytologically confirmed advanced or metastatic GC or gastroesophageal junction adenocarcinoma that had progressed with first-line treatment were recruited and received apatinib 250 or 500 mg oral apatinib and chemotherapy regimens, including docetaxel, paclitaxel, tegafur, oxaliplatin, and capecitabine. Each treatment cycle was 28 days (4 weeks). During post-discontinuation follow-up, all patients were followed for survival [every 8 weeks (+0 to 7 days)] until disease progression, death, or study completion. Overall survival (OS) was the primary endpoint. Secondary endpoints were overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Adverse events (AEs) were also noted. Tumor response and progression were assessed according to RECIST 1.1. AEs were graded following the National Cancer Institute common terminology criteria for AEs (NCI-CTCAE 4.0).ResultsBetween August 31, 2016 and February 17, 2020, a total of 32 patients were enrolled in the present study, and 29 were evaluable. At the time of data cut-off, median follow-up was 7.00 months (IQR, 4.60-12.23 months). The ORR and DCR were 18.52% and 92.59%, respectively. The median PFS was 3.06 months, and the median OS was 6.93 months. In the population receipt of apatinib plus docetaxel, the median OS was 6.51 months. AEs were observed in 22 patients. Leukopenia was the most common AE (24.1%), followed by hypertension (24.1%) and neutropenia (17.2%). Patients did not develop any AEs that were grade 4 or higher.ConclusionsThe combination of apatinib and chemotherapy demonstrated clinical activity and acceptable toxicity as a second-line treatment for advanced GC, and may provide new second-line treatment options for advanced GC patients.

Dataset Information

Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2).

Publications

Clinical and biomarker analyses of sintilimab versus chemotherapy as second-line therapy for advanced or metastatic esophageal squamous cell carcinoma: a randomized, open-label phase 2 study (ORIENT-2).

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