Induction chemotherapy followed by definitive chemoradiotherapy versus chemoradiotherapy alone in esophageal squamous cell carcinoma: a randomized phase II trial

Shiliang Liu, Liling Luo, Lei Zhao, Yujia Zhu, Hui Liu, Qiaoqiao Li, Ling Cai, Yonghong Hu, Bo Qiu, Li Zhang, Jingxian Shen, Yadi Yang, Mengzhong Liu, Mian Xi, Shiliang Liu, Liling Luo, Lei Zhao, Yujia Zhu, Hui Liu, Qiaoqiao Li, Ling Cai, Yonghong Hu, Bo Qiu, Li Zhang, Jingxian Shen, Yadi Yang, Mengzhong Liu, Mian Xi

Abstract

This randomized phase II trial aims to compare the efficacy and safety of induction chemotherapy followed by definitive chemoradiotherapy (CRT) versus CRT alone in patients with esophageal squamous cell carcinoma (ESCC) unsuitable for surgery (N = 110). The primary outcome was overall response rate (ORR), whereas the secondary outcome was overall survival. This trial did not meet pre-specified endpoints. The ORR was 74.5% in the induction chemotherapy group versus 61.8% in the CRT alone group (P = 0.152). The 3-year overall survival rate was 41.8% in the induction chemotherapy group and 38.1% in the CRT alone group (P = 0.584; hazard ratio, 0.88; 95% CI, 0.54-1.41). Grade 3-5 adverse events were similar. Patients who responded to induction chemotherapy had improved survival in the post-hoc analysis. These results demonstrate no improvement in response rate or survival with the addition of induction chemotherapy to CRT in unselected patients with ESCC. Trial number: NCT02403531.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1. CONSORT diagram of patient flow.
Fig. 1. CONSORT diagram of patient flow.
This figure shows reasons for exclusion from the study and the numbers of patients included in the analyses.
Fig. 2. Kaplan–Meier estimates of survival curves…
Fig. 2. Kaplan–Meier estimates of survival curves for the two treatment groups.
a Overall survival; b progression-free survival. IC + CRT induction chemotherapy followed by concurrent chemoradiotherapy, CRT chemoradiotherapy alone. Log-rank test was used (2-sided). Source data are provided as a Source Data file.
Fig. 3. Forest plots of treatment effects…
Fig. 3. Forest plots of treatment effects on overall survival within subgroups.
Squares represent the cohort-specific hazards ratios with error bars corresponding to 95% CI bounds, which were calculated by using the univariate Cox regression model. Source data are provided as a Source Data file.
Fig. 4. Kaplan–Meier analysis of overall survival…
Fig. 4. Kaplan–Meier analysis of overall survival in the two treatment groups stratified by clinical TNM stage.
a II, b III/IVA. Log-rank test was used (2-sided). Source data are provided as a Source Data file.
Fig. 5. Kaplan–Meier estimates of survival curves…
Fig. 5. Kaplan–Meier estimates of survival curves based on the clinical response to induction chemotherapy.
a Overall survival; b progression-free survival. IC induction chemotherapy, CRT chemoradiotherapy. Source data are provided as a Source Data file.

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