Sintilimab in patients with advanced esophageal squamous cell carcinoma refractory to previous chemotherapy: A randomized, open-label phase II trial (ORIENT-2).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4511-4511 ◽  
Author(s):  
Jianming Xu ◽  
Yi Li ◽  
Qingxia Fan ◽  
Yongqian Shu ◽  
Zhijun Wu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Treatment Options ◽  
Objective Response ◽  
First Line ◽  
Open Label ◽  
Phase 2 Trial ◽  
Line Chemotherapy

4511 Background: Patients (pts) with advanced esophageal squamous cell carcinoma (ESCC) refractory to first-line chemotherapy have limited treatment options. The study aims to evaluate the efficacy and safety of sintilimab, a PD-1 inhibitor, versus chemotherapy in these pts, and explore predictive value of PD-L1 and neutrophil-to-lymphocyte ratio (NLR) on efficacy of sintilimab. Methods: The open-label, multi-center phase 2 trial (NCT03116152) enrolled advanced ESCC pts refractory to first-line chemotherapy, and randomly assigned (1:1) them to receive sintilimab (200mg, Q3W) or chemotherapy (paclitaxel, 175mg/m2, Q3W; or irinotecan, 180mg/m2, Q2W), intravenously. The primary endpoint was overall survival (OS). Explorative endpoint were effects of PD-L1 and NLR on efficacy of sintilimab. Results: From May 16, 2017 to Aug 30, 2018, 190 pts were randomly assigned to sintilimab or chemotherapy (n = 95 per group). With the median follow-up of 7.2 months for sintilimab group and 6.2 months for chemotherapy group, the median OS in sintilimab was significantly higher than chemotherapy (7.2m vs. 6.2m, hazard ratio [HR] 0.70, P = 0.034). The objective response rate (ORR) was greater in sintilimab than chemotherapy with 12.6% vs. 6.3%, and the median duration of response was longer (8.3m vs. 6.2m). Incidences of treatment-related adverse events (TRAEs) of any grade (54.3% vs. 90.8%) and of grade 3-5 (20.2% vs. 39.1%) were both numerically less in sintilimab than in chemotherapy. The ORR in sintilimab versus chemotherapy in pts with tumor PD-L1 tumor proportion score (TPS) ≥1% and with TPS ≥10% were 20.2% vs. 0%, and 35.7% vs. 0%, respectively. In sintilimab group, pts with low NLR ( < 3) had a significant longer median OS (HR 0.54, P = 0.019) than with high NLR. Conclusions: Sintilimab was superior to chemotherapy with a significantly prolonged survival benefit and a favorable safety profile in pts with advanced ESCC refractory to first-line chemotherapy. High tumor PD-L1 expression (TPS ≥1% or ≥10%) might indicate more response benefit to sintilimab for these pts, and low NLR might be a positive predictive factor for sintilimab. Clinical trial information: NCT03116152 .

scholarly journals 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 trial (ORIENT-2)

2021 ◽  
Author(s):  
Jian Ming Xu ◽  
Yi Li ◽  
Qingxia Fan ◽  
Yongqian Shu ◽  
Lei Yang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Trial ◽  
Open Label Phase

Abstract This randomized, open-label, multi-center phase 2 study (ClinicalTrials.gov, number NCT03116152) assessed sintilimab, a PD-1 inhibitor, versus chemo in patients with advanced esophageal squamous cell carcinoma (ESCC) refractory to first-line (1L) chemotherapy. The primary endpoint was overall survival (OS), while exploratory endpoint was the association of biomarkers with treatment efficacy. The median OS in the sintilimab group was significantly prolonged compared with that of the chemotherapy group, (objective response rates 12.6% and 6.3 %, respectively). 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 TCR clonality and low mTBI showed the longest median OS (15.0 mo), while patients with low NLR at 6 wk post-treatment had a significantly prolonged median OS compared with those with high NLR. High expression of T-follicular helper cells or activated B-cell signature was significantly associated with longer progression-free survival in the sintilimab group.

scholarly journals Clinical efficacy and safety of apatinib combined with S-1 in advanced esophageal squamous cell carcinoma

2019 ◽  
Vol 38 (2) ◽  
pp. 500-506 ◽  
Author(s):  
Jian Zhao ◽  
Junmei Lei ◽  
Junyan Yu ◽  
Chengyan Zhang ◽  
Xuefeng Song ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Combination Therapy ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Efficacy ◽  
Squamous Cell ◽  
Objective Response ◽  
Efficacy And Safety ◽  
First Line ◽  
Line Chemotherapy

Summary Background Esophageal cancer is a very common malignant tumor in China, especially esophageal squamous cell carcinoma (ESCC), but there is currently no effective treatment for patients after first-line chemotherapy failure. Apatinib has shown promising outcomes in treatment with various solid tumors. Objectives To evaluate the clinical efficacy and safety of apatinib combined with S-1 in the treatment of advanced ESCC patients after first-line chemotherapy failure. Methods In this prospective study, fifteen patients with advanced ESCC who failed first-line chemotherapy were enrolled from Nov 2016 to Apr 2019. Patients received the combination therapy with apatinib (250-500 mg, once daily) plus S-1 (40–60 mg based on body surface area, twice daily). Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR). Adverse events (AEs) were recorded to evaluate the safety. Results A total of 12 patients were included in the efficacy analysis. The median PFS was 6.23 months, and the median OS was 8.83 months. Two (16.67%) patients achieved partial remission, 9 patients (75.00%) achieved stable disease and 1 (8.33%) patient achieved progressive disease. DCR and ORR was 91.67%and 16.67%, respectively. Most frequent AEs were hypertension, myelosuppression, weakness, hemorrhage, hand-foot syndrome, total bilirubin elevation, sick, proteinuria, oral ulcer, loss of appetite, and transaminase elevation. The most AEs were in grade I~II. Conclusion The combination therapy of apatinib plus S-1 was effective and well tolerated in the treatment of advanced ESCC patients after first-line chemotherapy failure. The combination therapy has the potential to be a potent therapeutic option for advanced ESCC patients after first-line chemotherapy failure.

scholarly journals Anti-PD1/PDL1 antibodies plus chemotherapy as first-line treatment for advanced esophageal squamous cell carcinoma

2020 ◽  
Author(s):  
Jiong Qian ◽  
Wu Lin ◽  
Haohao Wang ◽  
Chenyu Mao ◽  
Haiping Jiang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Objective Response ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Abstract Background: Patients with advanced esophageal squamous cell carcinoma (ESCC) have a poor prognosis with few treatment options. Immunotherapy was suggested as a promising treatment for ESCC from some clinical trials. Here we collected clinical results from 23 patients who were received anti-PD1/PDL1 antibodies (mAbs) plus chemotherapy as first line therapy with advanced ESCC, to analyze this combined therapy’s efficacy on advanced ESCC. Methods: Results of 23 Patients started treatment from December 15th, 2017 to September 27th, 2019 (12 patients were enrolled in phase II clinical trials, 11 patients were treated by physician’s choice regiment) of anti-PD1/PDL1 antibodies (mAbs) plus chemotherapy on advanced ESCC as first line treatment were collected. Regiments were either anti-PD1 or anti-PDL1 mAbs plus traditional chemotherapy (cisplatin/5-fluorouracil (5-FU), Paclitaxel/ cisplatin, Paclitaxel/carboplatin or Paclitaxel/ 5-FU) every 3 weeks for six cycles, followed by maintenance therapy with anti-PD1/PDL1 mAbs. Objective response and safety profiles were observed as well as progression-free survival(PFS), overall survival(OS) and duration of response. Results: Of the 23 patients, 18 (78.3%) responded to treatment: 15 partial and 3 complete response. 4 patients had stable disease and 1 patient had progressive disease. The median time to response was 1.4 months (range, 1.4 months – 2.8 months). Treatment-related adverse events occurred in all patients but 3-4 grade immune-mediated adverse events occurred in only one patient. As of April 10th, 2020, the Objective response rate was 78.3%, the median PFS was 15.5 months and the median OS was 21.5 months. No treatment-related deaths were observed. Conclusions: Anti-PD1/PDL1 antibodies plus chemotherapy as the first-line treatment for advanced ESCC showed promising results with manageable adverse events and worthy of further study.

scholarly journals Real-world effectiveness of second-line Afatinib versus chemotherapy for the treatment of advanced lung squamous cell carcinoma in immunotherapy-naïve patients

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
You-Yi Chen ◽  
Shih-Chieh Chang ◽  
Cheng-Yu Chang ◽  
Chun-Fu Chang ◽  
Yi-Chun Lai ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Real World ◽  
Treatment Options ◽  
Objective Response ◽  
Locally Advanced ◽  
Lung Squamous Cell Carcinoma ◽  
Second Line ◽  
Line Chemotherapy

Abstract Background Limited treatment options exist for relapsed advanced lung squamous cell carcinoma (SCC), leading to poor outcomes compared with adenocarcinoma. This study aimed to investigate the efficacy of second-line afatinib versus chemotherapy in patients with advanced lung SCC who progressed after first-line chemotherapy. Methods In this retrospective, multisite cohort study, we recruited patients with initial locally advanced or metastatic lung SCC from four institutes in Taiwan between June 2014 and October 2020. The primary endpoint of this study was progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and overall survival (OS). Results The present study enrolled 108 patients: 19 received second-line afatinib, and 89 received second-line chemotherapy. The median ages were 71 and 67 years, respectively. PFS was significantly longer among patients who received afatinib than among those who received chemotherapy (median 4.7 months [95% confidence interval (CI), 0.1–7.5] vs. 2.6 months [95% CI, 0.9–6.7]; hazard ratio (HR) 0.53 [95% CI 0.32–0.88], p = 0.013). Compared with the chemotherapy group, OS was longer in the afatinib group but did not reach significance (median 16.0 months [95% CI, 6.1–22.0] vs. 12.3 months [6.2–33.9]; HR 0.65 [95% CI 0.38–1.11], p = 0.112). Conclusions Afatinib offered a longer PFS and comparable OS to chemotherapy in advanced lung SCC patients in a real-world setting, it may be considered as a 2nd line alternative treatment choice for immunotherapy unfit advanced lung SCC patients.

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