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Cetuximab Maintenance Therapy in Patients with Unresectable Wild-Type RAS and BRAF Metastatic Colorectal Cancer: A Single-Institute Prospective Study

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Abstract

Introduction

Cetuximab plus FOLFIRI (leucovorin, fluorouracil, and irinotecan) is the preferred first-line therapy for RAS and BRAF wild-type (RBWT) metastatic colorectal cancer (mCRC). To counter chemotherapy-induced side effects, use of maintenance therapy is suggested. Therefore, we evaluated the efficacy and safety of cetuximab maintenance therapy in patients after effective completion of first-line induction therapy.

Methods

This prospective study enrolled untreated patients with mCRC RBWT who received first-line cetuximab plus FOLFIRI therapy. Following this, patients with treatment response either entered observation (stop treatment) or maintenance treatment 1 (cetuximab plus irinotecan) groups. After 6–12 cycles of maintenance treatment 1, patients entered maintenance treatment 2 (cetuximab only). If a patient progressed on maintenance 2, cetuximab plus FOLFIRI was reintroduced. The primary end point was failure-free survival (FFS), whereas the secondary end points included disease control rate (DCR), objective remission rate (ORR), and progression-free survival (PFS). Safety events were also evaluated.

Results

Among 79 enrolled patients, 72 completed first-line treatment effectively (DCR 91.1%, ORR 63.9%) and 44 entered maintenance 1 [median PFS 1 (mPFS, maintenance 1) 6.1 months, 95% confidence interval (CI) 6.0–6.2; DCR 56.8%; ORR 22.7%]. Of them, 21 entered maintenance treatment 2 (mPFS2 8.7 months, 95% CI 3.3–14.1; DCR 28.6%; ORR 4.8%). Median FFS (mFFS) was significantly longer in the maintenance 1 group compared with the observation group [12.7 vs. 3.0 months; hazard ratio (HR) 0.202, 95% CI 0.111–0.369; P < 0.001]. Overall, mFFS was 19.0 and 9.3 months in maintenance and observation groups, respectively (HR 0.211, 95% CI 0.117–0.380; P < 0.001). Rash acneiform, mucositis, and asthenia were commonly observed adverse events during maintenance treatment.

Conclusion

Maintenance treatment with cetuximab after first-line therapy significantly improved FFS, with an acceptable safety profile in untreated patients with mCRC RBWT.

Trial Registration

Retrospectively registered, 2019/10/02, Chinese Clinical Trial Registry, ChiCTR number 1900026360.

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Acknowledgements

We thank all the participants of this study.

Funding

The study was funded by the Joint Funds for the innovation of science and technology Fujian province (2018Y9031, 2018Y9032) and Fujian Medical University Qihang Foundation (2018QH1035). Sponsors of the study also funded the journal’s Rapid service fee.

Medical Writing Assistance

Medical writing support under authors’ direction was provided by Priyanka Bannikoppa, PhD, and Anuradha Nalli, PhD (Indegene Pvt. Ltd., Bangalore), as funded by the author.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Prior Presentation

The abstract was submitted to ASCO, 2019 held in Chicago from May 31–June 4.

Disclosures

Tao Jing, Hao Chen, Xiaoyan Lin, Jianwei Zheng, Bin Du, Baoyu Yang, Qing Liu, Dongta Zhong, Xinli Wang, Han Wang, Mengxin Lin, Jinhuo Lai and Peifeng Hou have nothing to disclose.

Compliance with Ethics Guidelines

This study was conducted in accordance with the Declaration of Helsinki, 1964, as revised in 2013 and the International Council for Harmonization guideline E6: Good Clinical Practice (GCP). The study was approved by the Institutional Review Board (IRB number: 2015KY033) of Fujian Medical University Union Hospital and the investigators obtained informed consent from each patient. The study protocol was registered at Chinese Clinical Trial Registry, ChiCTR number 1900026360.

Data Availability

All data generated or analyzed during this study are included in this published article/as supplementary information files.

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Author notes

  1. Tao Jiang and Hao Chen contributed equally to this article.

Authors and Affiliations

  1. Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, 350001, People’s Republic of China

    Tao Jiang, Hao Chen, Jianwei Zheng, Bin Du, Baoyu Yang, Qing Liu, Dongta Zhong, Xinli Wang, Han Wang, Mengxin Lin, Jinhuo Lai, Peifeng Hou & Xiaoyan Lin

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  1. Tao Jiang
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Correspondence to Xiaoyan Lin.

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Jiang, T., Chen, H., Zheng, J. et al. Cetuximab Maintenance Therapy in Patients with Unresectable Wild-Type RAS and BRAF Metastatic Colorectal Cancer: A Single-Institute Prospective Study. Adv Ther 37, 2829–2840 (2020). https://doi.org/10.1007/s12325-020-01360-8

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