Dataset Information

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study.

ABSTRACT: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m²] plus docetaxel [25 mg/m²] for 4 weeks) and radiotherapy (2.0 Gy/fraction, total 60 Gy) with camrelizumab (200 mg every 2 weeks for 32 weeks). Primary endpoints were safety and tolerability, and health-related quality of life. Secondary endpoints were radiological and pathological response rates, overall survival (OS), and progression-free survival (PFS). Candidate biomarkers in tumor and peripheral blood were monitored at baseline and after 40 Gy radiation. Twenty patients were enrolled. The most common treatment-related grade 3 adverse events included radiation esophagitis (20%) and esophageal fistula (10%). Serious treatment-related adverse events occurred in eight (40%) patients. No treatment-related deaths were reported. Health-related quality of life did not deteriorate. Thirteen (65%) patients had an objective response after 40 Gy radiation. At a median follow-up of 23.7 months (95% CI 21.9-24.5), OS and PFS time ranged from 8.2-28.5 and 4.0-28.5 months, respectively. The 12-month and 24-month OS rate was 85.0% and 69.6%; PFS rate was 80.0% and 65.0%. Tumor PD-L1 expression and CD11c⁺ dendritic cells and peripheral-blood IL-27, IL-15, Eotaxin-3, and IL-22 were associated with OS. First-line concurrent chemoradiotherapy plus camrelizumab had a manageable safety profile and promising antitumour efficacy for ESCC, and deserves further study.

SUBMITTER: Zhang W

PROVIDER: S-EPMC8489938 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study.

Zhang Wencheng W Yan Cihui C Zhang Tian T Chen Xi X Dong Jie J Zhao Jingjing J Han Dong D Wang Jun J Zhao Gang G Cao Fuliang F Zhou Dejun D Jiang Hongjing H Tang Peng P Zhao Lujun L Yuan Zhiyong Z Wang Quanren Q Wang Ping P Pang Qingsong Q

Oncoimmunology 20210928 1

Patients with locally advanced esophageal squamous cell carcinoma (ESCC) show poor survival after concurrent chemoradiotherapy. This study investigated the safety and feasibility of combining concurrent chemoradiotherapy with the anti-PD-1 antibody camrelizumab as first-line treatment for these patients. In this phase 1b study (ClinicalTrials.gov NCT03671265), patients received concurrent chemotherapy (cisplatin [25 mg/m<sup>2</sup>] plus docetaxel [25 mg/m<sup>2</sup>] for 4 weeks) and radiothe ...[more]

PMID: 34616588

Similar Datasets

Project description:Lessons learnedRadiotherapy plus anti-PD-1 antibody as first-line therapy is safe and feasible in locally advanced esophageal squamous cell carcinoma (ESCC). Tumor-infiltrating and peripheral lymphocytes were associated with patient survival. Further studies combining chemoradiotherapy with immunotherapy in locally advanced ESCC and exploration of predictive biomarkers are warranted.BackgroundWe conducted a phase Ib study of radiotherapy plus programmed cell death protein 1 (PD-1) monoclonal antibody camrelizumab as first-line treatment for locally advanced esophageal squamous cell carcinoma (ESCC).MethodsWe planned to enroll 20 patients with newly diagnosed locally advanced ESCC. Patients received 60 Gy radiation (2.0 Gy/fraction, 5 fractions/week), with camrelizumab (200 mg every 2 weeks) starting with radiotherapy and continuing for 32 weeks (i.e., for 16 cycles). The primary endpoints were safety and feasibility. Secondary endpoints were rates of radiologic and pathologic response, overall survival (OS), and progression-free survival (PFS). Study data were collected by the week during radiotherapy (RT), every month during the maintenance camrelizumab treatment, and every 3 months after treatment. Tumor microenvironment and peripheral blood were monitored at baseline and after 40 Gy radiation for association with efficacy.ResultsTwenty patients were enrolled and received treatment. One patient (patient 10) was excluded upon discovery of a second tumor in the bladder during treatment, leaving 19 patients for analysis. Toxicity was deemed tolerable. Fourteen (74%) patients had assessed objective response. At a median follow-up time of 31.0 months (95% confidence interval [CI], 27.0-35.1), median OS and PFS times were 16.7 months (95% CI, 5.9-27.9) and 11.7 months (95% CI, 0-30.3), respectively. OS and PFS rates at 24 months were 31.6% and 35.5%, respectively. Kaplan-Meier analysis revealed associations between the following factors and OS/PFS: tumor programmed cell death ligand 1 (PD-L1) expression, PD-1+ CD8+ , PD-1+ CD4+ T cells, and PD-L1+ CD4+ T cells; peripheral blood CD4+ , CD8+ , CD4+ regulatory T cells, and their subsets.ConclusionRadiotherapy plus camrelizumab had manageable toxicity and antitumor efficacy for locally advanced ESCC. Several biomarkers were associated with clinical benefit and deserve further study.

Project description:BackgroundCamrelizumab combined with chemotherapy has shown significant clinical benefits in the first-line treatment of advanced esophageal squamous cell cancer (ESCC). Despite promising results from randomized trials, there is a need for real-world evidence to understand the broader applicability and long-term outcomes of neoadjuvant treatments in diverse patient populations with ESCC. This study aimed to evaluate the efficacy and safety of neoadjuvant camrelizumab combined with chemotherapy in patients with resectable locally advanced ESCC in a real-world setting.MethodsWe retrospectively reviewed clinical data from 83 patients with locally advanced, potentially resectable ESCC who received neoadjuvant camrelizumab combined with docetaxel, oxaliplatin, and S1 chemotherapy at Xijing Hospital of Digestive Diseases, Fourth Military Medical University from March 2020 to May 2023. Inclusion criteria were based on clinical stage, histological confirmation, and patient tolerance. Baseline clinical characteristics were assessed using standard diagnostic tools. Treatment involved three cycles of camrelizumab combined with chemotherapy, with efficacy and safety evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Tumor downstaging, survival outcomes, and safety were assessed.ResultsThe median age of patients was 61 years (range, 46-75 years), and tumors were predominantly located in the middle (n=49, 59.04%) and lower (n=23, 27.71%) regions of the esophagus. Most patients were diagnosed at stages III-IV (55.42% and 38.55%, respectively), and all of the patients completed neoadjuvant treatment. Additionally, 24 (28.92%) patients achieved complete response (CR), 40 (48.19%) patients achieved partial response (PR), and 9 (10.84%) patients achieved stable disease (SD). The objective response rate (ORR) was 77.11% (64/83), and the disease control rate (DCR) was 87.95% (73/83). Of the 14 patients who underwent surgery, the R0 resection rate was 100%, and 28.57% (4/14) achieved pathological CR (pCR). The median follow-up time was 31.0 months, and the 3-year overall survival (OS) rate was 56.9%. The incidence of grade ≥3 adverse events was 6.02% (5/83). No deaths occurred.ConclusionsWhile our real-world data suggest potential benefits of neoadjuvant camrelizumab plus chemotherapy in locally advanced ESCC, the absence of a control group limits the generalizability of these findings. Further randomized studies are needed to validate these results.

Project description:BackgroundPatients with locally advanced esophageal cancer who are treated with trimodality therapy have a high recurrence rate. Preclinical evidence suggests that inhibition of cyclooxygenase 2 (COX2) increases the effectiveness of chemoradiation, and observational studies in humans suggest that COX-2 inhibition may reduce esophageal cancer risk. This trial tested the safety and efficacy of combining a COX2 inhibitor, celecoxib, with neoadjuvant irinotecan/cisplatin chemoradiation.MethodsThis single arm phase 2 trial combined irinotecan, cisplatin, and celecoxib with concurrent radiation therapy. Patients with stage IIA-IVA esophageal cancer received weekly cisplatin 30 mg/m(2) plus irinotecan 65 mg/m(2) on weeks 1, 2, 4, and 5 concurrently with 5040 cGy of radiation therapy. Celecoxib 400 mg was taken orally twice daily during chemoradiation, up to 1 week before surgery, and for 6 months following surgery.ResultsForty patients were enrolled with stage IIa (30 %), stage IIb (20 %), stage III (22.5 %), and stage IVA (27.5 %) esophageal or gastroesophageal junction cancer (AJCC, 5th Edition). During chemoradiation, grade 3-4 treatment-related toxicity included dysphagia (20 %), anorexia (17.5 %), dehydration (17.5 %), nausea (15 %), neutropenia (12.5 %), diarrhea (10 %), fatigue (7.5 %), and febrile neutropenia (7.5 %). The pathological complete response rate was 32.5 %. The median progression free survival was 15.7 months and the median overall survival was 34.7 months. 15 % (n = 6) of patients treated on this study developed brain metastases.ConclusionsThe addition of celecoxib to neoadjuvant cisplatin-irinotecan chemoradiation was tolerable; however, overall survival appeared comparable to prior studies using neoadjuvant cisplatin-irinotecan chemoradiation alone. Further studies adding celecoxib to neoadjuvant chemoradiation in esophageal cancer are not warranted.Trial registrationClinicaltrials.gov: NCT00137852 , registered August 29, 2005.

Project description:BackgroundCamrelizumab and chemotherapy demonstrated durable antitumor activity with a manageable safety profile as first-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the safety and efficacy of camrelizumab plus neoadjuvant chemotherapy, using pathologically complete response (pCR) as primary endpoint, in the treatment for locally advanced ESCC.MethodsPatients with locally advanced but resectable thoracic ESCC, staged as T1b-4a, N2-3 (≥3 stations), and M0 or M1 lymph node metastasis (confined to the supraclavicular lymph nodes) were enrolled. Eligible patients received intravenous camrelizumab (200 mg, day 1) plus nab-paclitaxel (100 mg/m2, day 1, 8, 15) and carboplatin (area under curve of 5 mg/mL/min, day 1) of each 21-days cycle, for two cycles before surgery. The primary endpoint is pCR rate in the per-protocol population. Safety was assessed in the modified intention-to-treat population that was treated with at least one dose of camrelizumab.ResultsFrom November 20, 2019 to December 22, 2020, 60 patients were enrolled. 55 (91.7%) patients completed the full two-cycle treatment successfully. 51 patients underwent surgery and R0 resection was achieved in 50 (98.0%) patients. pCR (ypT0N0) was identified in 20 (39.2%) patients and 5 (9.8%) patients had complete response of the primary tumor but residual disease in lymph nodes alone (ypT0N+). 58 patients (96.7%) had any-grade treatment-related adverse events (TRAEs), with the most common being leukocytopenia (86.7%). 34 patients (56.7%) had adverse events of grade 3 or worse, and one patient (1.7%) occurred a grade 5 adverse event. There was no in-hospital and postoperative 30-day as well as 90-day mortality.ConclusionsThe robust antitumor activity of camrelizumab and chemotherapy was confirmed and demonstrated without unexpected safety signals. Our findings established camrelizumab and chemotherapy as a promising neoadjuvant treatment for locally advanced ESCC.Trial registration numberChiCTR1900026240.

Dataset Information

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study.

Publications

Addition of camrelizumab to docetaxel, cisplatin, and radiation therapy in patients with locally advanced esophageal squamous cell carcinoma: a phase 1b study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets