Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer (ESWN 01): a prospective randomized, multicenter, open-labeled phase 3 trial

Jing Huang†Email author View ORCID ID profile,
Binghe Xu†Email author,
Ying Liu,
Junxing Huang,
Ping Lu,
Yi Ba,
Lin Wu,
Yuxian Bai,
Shu Zhang,
Jifeng Feng,
Ying Cheng,
Jie Li,
Lu Wen,
Xianglin Yuan,
Changwu Ma,
Chunhong Hu,
Qingxia Fan and
Xi Wang

†Contributed equally

Cancer Communications201939:16

https://doi.org/10.1186/s40880-019-0359-7

Received: 11 September 2018
Accepted: 19 March 2019
Published: 2 April 2019

Abstract

Background

The benefit of systemic treatments in esophageal squamous cell carcinoma (ESCC) which has progressed after chemotherapy is still uncertain and optimal regimens based on randomized trials have not yet been established. We aimed to compare the efficacy of irinotecan plus S-1 with S-1 monotherapy in recurrent or metastatic ESCC patients who had resistance to platinum- or taxane-based chemotherapy.

Methods

We conducted a prospective randomized, multicenter, open-label, phase 3 trial in 15 centers across China. Eligible patients were adults with histologically confirmed recurrent or metastatic ESCC, and were randomly assigned (ratio, 1:1) to receive either irinotecan plus S-1 (intravenous infusion of irinotecan [160 mg/m2] on day 1 and oral S-1 [80–120 mg] on days 1–10, repeated every 14 days) or oral S-1 monotherapy (80–120 mg/day on days 1–14, repeated every 21 days) using a central computerized minimization procedure. The primary endpoint was progression-free survival (PFS).

Results

Between December 23, 2014 and July 25, 2016, we screened 148 patients and randomly assigned 123 patients to receive either irinotecan plus S-1 regimen (n = 61) or S-1 monotherapy (n = 62). After a median follow-up of 29.2 months (95% confidence interval [CI] 17.5–40.9 months), the median PFS was significantly longer in the irinotecan plus S-1 group than in the S-1 monotherapy group (3.8 months [95% CI 2.9–4.3 months] vs. 1.7 months [95% CI 1.4–2.7 months], hazard ratio = 0.58, 95% CI 0.38–0.86, P = 0.006). The objective response rates were 24.6% in the irinotecan plus S-1 group and 9.7% in the S-1 monotherapy group (P = 0.002). The patients in the irinotecan plus S-1 group presented with increased rates of grade 3–4 leukopenia (16.4% vs. 0%), neutropenia (14.8% vs. 1.6%), and nausea (4.9% vs. 0%). No significant difference in grade 3–4 diarrhea and no treatment-related deaths were observed in both groups.

Conclusions

The combination of irinotecan with S-1 was similarly tolerable but significantly prolonged PFS compared to S-1 monotherapy as a second- or third-line treatment in patients with recurrent or metastatic ESCC.

Clinical Trial Registration NCT02319187. Registered on December 9, 2014