Clinical Study

Chemoradiotherapy with extended nodal irradiation and/or erlotinib in locally advanced oesophageal squamous cell cancer: long-term update of a randomised phase 3 trial

Abstract

Background

To report the long-term outcomes of a phase III trial designed to test two hypotheses: (1) elective nodal irradiation (ENI) is superior to conventional field irradiation (CFI), and (2) chemoradiotherapy plus erlotinib is superior to chemoradiotherapy in locally advanced oesophageal squamous cell cancer (ESCC).

Methods

Patients with locally advanced ESCC were randomly assigned (1:1:1:1 ratio) to one of the four groups: A: radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel and cisplatin) plus erlotinib; B: radiotherapy adoption of ENI with two cycles of concurrent TP; C: radiotherapy adoption of CFI with two cycles of concurrent TP plus erlotinib and D: radiotherapy adoption of CFI with two cycles of concurrent TP. A total of 60 Gy of radiation doses was delivered over 30 fractions. We explored the impact of epidermal growth factor receptor (EGFR) expression on the efficacy of erlotinib plus chemoradiotherapy.

Results

A total of 352 patients (88 assigned to each treatment group) were enrolled. The 5-year survival rates were 44.9%, 34.8%, 33.8% and 19.6% in groups A, B, C and D, respectively (P = 0.013). ENI significantly improved OS compared with standard CFI (median, 38.5 vs 22.6 months; HR, 0.74; P = 0.018). The addition of erlotinib significantly improved OS (median, 39.4 vs 27.4 months; HR, 0.75; P = 0.025). Patients with overexpressing EGFR treated with erlotinib had a better OS and PFS than those without erlotinib.

Conclusions

Concurrent chemoradiotherapy with ENI and/or erlotinib improved long-term survival in locally advanced ESCC.

Clinical trial registration

Trial registration: NCT00686114.

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Fig. 1: Flow diagram.
Fig. 2: Overall survival in the intention-to-treat population.
Fig. 3: Progression-free survival in the intention-to-treat population.
Fig. 4: Overall survival stratified by EGFR expression status.

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Acknowledgements

We appreciate the critical review comments from Feng-Ming (Spring) Kong, MD, PhD, FACR, FASTRO. We thank all participating patients and the principal investigators and their institutions for their contributions to this study.

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Authors

Contributions

C.X., Z.J. and H.L. had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. S.W. and L.W. contributed to the conception and design of the study; C.X., Z.J., H.L., W.J. and L.M. performed the data analysis; C.X. drafted the article; W.H., A.Z., D.L., L.D., H.Z., C.X., X.L., D.D., M.C., X.B., B.T. and B.X. interpreted the results; W.H., A.Z., D.L., L.D., H.Z., C.X., X.L., D.D., M.C., X.B., B.T., B.X., R.X. and Q.L. acquired data and revised the manuscript. All authors have read and approved the manuscript and S.W. took responsibility for submitting the manuscript for publication.

Corresponding authors

Correspondence to Lvhua Wang or Shixiu Wu.

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Ethics approval and consent to participate

The study was performed in accordance with the Declaration of Helsinki. All patients provided written informed consent, and the study was approved by the institutional review board of First Affiliated Hospital of Wenzhou Medical University, Hangzhou Cancer Hospital, No. 1 People’s Hospital of Huaian, Cancer Hospital Chinese Academy of Medical Sciences, Taizhou Hospital of Zhejiang Province, Anyang Cancer Hospital, The First Affiliated Hospital of Bengbu Medical College, Anhui Provincial Hospital, Zhongnan Hospital of Wuhan University, Kaohsiung Medical University Hospital Cancer Centre, Central Hospital of Lishui City, Zhejiang Cancer Hospital, Jiangsu Cancer Hospital, Affiliated Hospital of North Sichuan Medical College and Sun Yat-Sen University Cancer Center.

Consent for publication

Consent for publication was obtained from all patients prior to sample collection.

Data availability

All data generated or analysed during this study are available from the corresponding authors upon reasonable request.

Competing interests

The authors declare no competing interests.

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No commercial support was provided for this study.

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Xie, C., Jing, Z., Luo, H. et al. Chemoradiotherapy with extended nodal irradiation and/or erlotinib in locally advanced oesophageal squamous cell cancer: long-term update of a randomised phase 3 trial. Br J Cancer (2020). https://doi.org/10.1038/s41416-020-01054-6

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