Dataset Information

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

ABSTRACT:

Importance

Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed.

Objective

To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer.

Design, setting, and participants

A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021.

Interventions

Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone.

Main outcomes and measures

The primary end point was the 2-year overall survival rate using intention-to-treat analysis.

Results

Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group.

Conclusions and relevance

In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer.

Trial registration

ClinicalTrials.gov Identifier: NCT02813967.

SUBMITTER: Ji Y

PROVIDER: S-EPMC8343504 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Publications

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

Ji Yongling Y Du Xianghui X Zhu Weiguo W Yang Yanguang Y Ma Jun J Zhang Li L Li Jiancheng J Tao Hua H Xia Jianhong J Yang Haihua H Huang Jin J Bao Yong Y Du Dexi D Liu Degan D Wang Xiusheng X Li Chaoming C Yang Xinmei X Zeng Ming M Liu Zhigang Z Zheng Wen W Pu Juan J Chen Jun J Hu Wangyuan W Li Peijing P Wang Jin J Xu Yujin Y Zheng Xiao X Chen Jianxiang J Wang Wanwei W Tao Guangzhou G Cai Jing J Zhao Jizhong J Zhu Jun J Jiang Ming M Yan Yan Y Xu Guoping G Bu Shanshan S Song Binbin B Xie Ke K Huang Shan S Zheng Yuanda Y Sheng Liming L Lai Xiaojing X Chen Ying Y Cheng Lei L Hu Xiao X Ji Wenhao W Fang Min M Kong Yue Y Yu Xiaofu X Li Huizhang H Li Runhua R Shi Lei L Shen Wei W Zhu Chaonan C Lv Junwei J Huang Rong R He Han H Chen Ming M

JAMA oncology 20211001 10

<h4>Importance</h4>Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed.<h4>Objective</h4>To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer.<h4>Design, setting, and participants</h4>A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2 ...[more]

PMID: 34351356

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Project description:ImportancePalliative radiotherapy (RT) is generally recommended for older patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis. A new combination treatment is therefore needed.ObjectiveTo assess the efficacy and toxicity of RT plus icotinib vs RT alone in older patients with ESCC.Design, setting, and participantsThis randomized, multicenter, open-label, phase II clinical trial was conducted in China, with enrollment between January 1, 2015, and October 31, 2016. Patients aged 70 years or older with clinical stage T2 to T4, N0/1, M0/1a unresectable (because of comorbidities, T4 disease, unresectable lymph node, or refused surgery) ESCC were randomized 1:1 to receive RT plus icotinib or RT alone. Radiation was prescribed at 60 Gy in 30 fractions in both groups, and icotinib was administered at a dosage of 125 mg 3 times a day in the RT plus icotinib group. The last follow-up was completed on June 30, 2019, and data were analyzed from July 1 to September 30, 2019.InterventionsPatients were randomized to either RT plus icotinib or RT alone.Main outcomes and measuresThe primary end point was overall survival (OS). Treatment-related toxic effects were evaluated. Immunohistochemistry was performed to analyze epidermal growth factor receptor (EGFR) expression if available.ResultsA total of 127 patients (median age, 76 years [range, 70-91 years]; 76 men [59.8%]) were enrolled and were eligible for survival analysis. Median OS was 24.0 (95% CI, 22.2-25.8) months in the RT plus icotinib group vs 16.3 (95% CI, 13.8-18.8) months in the RT group (hazard ratio, 0.53; 95% CI, 0.33-0.87; P = .008). No difference was observed in grades 3 or 4 adverse events. Patients with EGFR overexpression had a significantly better median overall survival (not reached vs 16.3 months [range, 2.6-45.1 months]; P = .03) in the RT plus icotinib group.Conclusions and relevanceIn this randomized clinical trial, icotinib plus RT was well tolerated and improved OS in older patients with ESCC relative to RT alone. Patients with EGFR overexpression benefitted more from icotinib with RT.Trial registrationClinicalTrials.gov Identifier: NCT02375581.

Project description:Purpose: The aim of this study was to evaluate the clinical benefit of different radiation doses in concurrent chemoradiotherapy (CCRT) for esophageal carcinoma using modern radiotherapy techniques. Methods: A systematic review was conducted by screening PubMed, EMBASE, Cochrane Central Register of Controlled Trials, SCOPUS, Wanfang, and Chinese National Knowledge Infrastructure (CNKI) databases with prespecified searching strategy. Studies which compared high radiation dose group with low-dose radiation group using modern radiotherapy techniques for esophageal cancer patients in CCRT were identified. The hazard ratios (HR) for overall survival (OS) and the odds ratios (OR) for local-regional failure (LRF), distant metastasis (DM), and toxicities were considered as the outcomes of interest. R 3.6.2 software was used for statistical analysis. Results: Twelve studies involving 10,896 patients were included for analyses. The results showed that the high-dose group had better OS (HR = 0.79, 95% CI = 0.70-0.90, P = 0.0004) and the local-regional control (OR = 0.59, 95% CI = 0.46-0.76, P < 0.0001), especially for patients who were diagnosed with squamous cell carcinoma (SCC). The subgroup analyses further indicated that ≥ circa 60 Gy can significantly improve the OS (HR = 0.73, 95% CI = 0.68-0.80, P < 0.0001) as well as the local-regional control (OR = 0.54, 95% CI = 0.40-0.74, P < 0.0001) as compared with < circa 60 Gy. Another subgroup analysis comparing ≤ 50.4 Gy with > 50.4 Gy showed no substantial difference in OS (HR = 0.98, 95% CI = 0.93-1.03, P = 0.43). In addition, there are no significant differences between the two groups in grade 3-5 radiation pneumonitis (OR = 1.05, 95% CI = 0.54-2.05, P = 0.89), grade 3-5 radiation esophagitis (OR = 1.40, 95% CI = 0.93-2.11, P = 0.11), treatment-related death (OR = 1.60, 95% CI = 0.70-3.66, P = 0.27), and DM (OR = 1.21, 95% CI = 0.92-1.59, P = 0.17). Conclusions: For esophageal carcinoma receiving CCRT with modern radiation techniques, evidence suggested that high-dose radiotherapy, especially ≥circa 60 Gy, had potentials to improve the OS and local-regional control without increase in severe toxicities when compared with low-dose radiotherapy. The result needs to be confirmed by randomized clinical trials.

Project description:BackgroundConcurrent chemoradiotherapy is the standard of care for locally advanced cervical cancer. Concurrent chemoradiotherapy with programmed blockade of the cell death-1/programmed cell death-ligand 1 pathway may promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, leading to enhanced immune-mediated tumor surveillance.Primary objectiveThe CALLA trial is designed to determine the efficacy and safety of the programmed cell death-ligand 1 blocking antibody, durvalumab, with and following concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in women with locally advanced cervical cancer.Study hypothesisDurvalumab concurrent with and following concurrent chemoradiotherapy will improve progression-free survival in patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2 to IVA cervical cancer compared with concurrent chemoradiotherapy alone.Trial designCALLA is a phase III, randomized, multicenter, international, double-blind, placebo-controlled study. Patients will be randomized 1:1 to receive either durvalumab (1500 mg intravenously (IV)) or placebo every 4 weeks for 24 cycles. All patients will receive external beam radiotherapy with cisplatin (40 mg/m2) IV or carboplatin (area under the curve 2) IV once a week for 5 weeks, followed by image-guided brachytherapy.Major inclusion/exclusion criteriaThe study will enroll immunotherapy-naïve adult patients with histologically confirmed cervical adenocarcinoma, cervical squamous, or adenosquamous carcinoma FIGO 2009 stages IB2-IIB node positive and stage IIIA-IVA with any node stage. Patients will have had no prior definitive surgical, radiation, or systemic therapy for cervical cancer.Primary endpointThe primary endpoint is progression-free survival (assessed by the investigator according to Response Evaluation Criteria in Solid Tumors v1.1, histopathological confirmation of local tumor progression or death).Sample sizeApproximately 714 patients will be randomized 1:1 to receive either durvalumab + concurrent chemoradiotherapy or placebo + concurrent chemoradiotherapy.Estimated dates for completing accrual and presenting resultsPatient enrollment is continuing globally with an estimated completion date of April 2024.Trial registrationNCT03830866.

Project description:BackgroundThe standard treatment for elderly patients with unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is definitive chemoradiotherapy with S-1. However, the 3-year overall survival (OS) is limited to approximately 40%. Tislelizumab is the first- and second-line standard treatment for advanced ESCC with tolerable toxicity. In this study, we aimed to explore a new curative strategy for locally advanced unresectable ESCC in the elderly by combining tislelizumab with chemoradiotherapy.MethodsThis study is an open-label, multicenter, investigator-initiated phase II clinical trial in older patients with inoperable locally advanced ESCC evaluating tislelizumab plus concurrent chemoradiotherapy compared with concurrent chemoradiotherapy. The main inclusion criteria were pathological confirmation of locally advanced inoperable ESCC at clinical cT1N2-3M0 or cT2-4bN0-3M0 (stage II-IVA), age ≥ 70 years, absence of previous systemic anti-tumor therapy, and adequate organ function. A total of 136 patients will be recruited from approximately seven centers (in Tianjin, Chengdu, Taiyuan, Zhengzhou, Shijiazhuang, Changsha, Nanjing) over a period of 18 months and randomized in a 1:1 ratio to receive tislelizumab in combination with concurrent chemoradiotherapy (tislelizumab + S-1 + radiotherapy) or concurrent chemoradiotherapy (S-1 + radiotherapy). The efficacy and safety of the treatment will be evaluated during the therapy and follow-up period until disease progression, death, or the end of the trial. The primary study endpoint was investigator-assessed progression-free survival (PFS), and secondary study endpoints were OS, objective response rate (ORR), duration of remission (DOR), and safety. Fresh or archival tumor tissues and peripheral blood samples will be used in exploratory studies.DiscussionThis study is the first "programmed death-1 (PD-1) inhibitor combined with concurrent chemoradiotherapy" for elderly patients with inoperable locally advanced ESCC (NCT06061146). The synergistic efficacy of combined definitive concurrent chemoradiotherapy with tislelizumab is expected to result in survival benefits for elderly patients with inoperable locally advanced ESCC. Because S-1 plus concurrent radiotherapy is the standard treatment option for locally advanced ESCC in older patients, the combination of definitive concurrent chemoradiotherapy and tislelizumab has the potential to change the standard ESCC therapeutic strategy with comparable safety.Trial registrationClinicalTrials.gov NCT06061146.Registered 9/10/2023.

Project description:ImportanceConcurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT).ObjectiveTo assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT.Design, setting, and participantsThis multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022.InterventionsPatients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]).Main outcomes and measuresThe primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms).ResultsAmong 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation.Conclusions and relevanceAmong patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy.Trial registrationClinicalTrials.gov Identifier: NCT02633202.

Project description:BACKGROUND:Preoperative chemoradiotherapy (CRT) followed by surgery is the most common approach for patients with resectable esophageal cancer. Nevertheless, considerable numbers of esophageal-cancer patients undergo surgery as the first treatment. The benefit of neoadjuvant therapy might only be for patients with a pathologic complete response, so stratified research is necessary. Postoperative treatments have important roles because of the poor survival rates of patients with stage-IIB/III disease treated with resection alone. Five-year survival of patients with stage-IIB/III thoracic esophageal squamous cell carcinoma (TESCC) after surgery is 20.0-28.4%, and locoregional lymph-node metastases are the main cause of failure. Several retrospective studies have shown that postoperative radiotherapy (PORT) and postoperative chemoradiotherapy (POCRT) after radical esophagectomy for esophageal carcinoma with positive lymph-node metastases and stage-III disease can decrease locoregional recurrence and increase overall survival (OS). Using intensity-modulated RT, PORT reduces locoregional recurrence further. However, the rate of distant metastases increases to 30.7%. Hence, chemotherapy may be vital for these patients. Therefore, a prospective randomized controlled trial (RCT) is needed to evaluate the value of PORT and concurrent POCRT in comparison with surgery alone (SA) for esophageal cancer. METHOD:This will be a phase-II/III RCT. The patients with pathologic stage-IIB/III esophageal squamous cell carcinoma will receive concurrent POCRT or PORT after radical esophagectomy compared with those who have SA. A total of 120 patients in each group will be recruited. POCRT patients will be 50.4 Gy concurrent with paclitaxel (135-150 mg/m2) plus cisplatin or nedaplatin (50-75 mg/m2) treatment every 28 days. Two cycles will be required for concurrent chemotherapy. The prescription dose will be 54 Gy for PORT. The primary endpoint will be disease-free survival (DFS). The secondary endpoint will be OS. Other pre-specified outcome measures will be the proportion of patients who complete treatment, toxicity, and out-of-field regional recurrence rate between PORT and POCRT. DISCUSSION:This prospective RCT will provide high-level evidence for postoperative adjuvant treatment of pathologic stage-IIB/III esophageal squamous cell carcinoma. TRIAL REGISTRATION:clinicaltrials.gov (NCT02279134). Registered on October 26, 2014.

Dataset Information

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

Importance

Objective

Design, setting, and participants

Interventions

Main outcomes and measures

Results

Conclusions and relevance

Trial registration

Publications

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

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