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Phase II Study of Third-Line Panitumumab Rechallenge in Patients with Metastatic Wild-Type KRAS Colorectal Cancer Who Obtained Clinical Benefit from First-Line Panitumumab-Based Chemotherapy: JACCRO CC-09

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Abstract

Background

Regorafenib and trifluridine/tipiracil are standard third-line chemotherapies for colorectal cancer patients, but their efficacy is limited. Anti-epidermal growth factor receptor antibody rechallenge has been reported to be promising for patients who have obtained clinical benefit from first-line cetuximab-based chemotherapy. Moreover, panitumumab showed non-inferior efficacy to cetuximab.

Objective

This study assessed the efficacy and safety of third-line panitumumab rechallenge in patients with metastatic KRAS exon 2 wild-type metastatic colorectal cancer who obtained clinical benefit from first-line panitumumab-based chemotherapy.

Patients and Methods

This was a prospective, multicenter, phase II trial conducted from October 2013 to August 2017. Major eligibility criteria included KRAS exon 2 wild-type and achievement of complete response, partial response, or continued stable disease for at least 6 months in first-line panitumumab-based therapy. Irinotecan plus panitumumab treatment was continued until disease progression or unacceptable toxicity was observed. The primary endpoint was the 3-month progression-free survival (PFS) rate.

Results

Twenty-five patients were enrolled in this study. Their median age was 66.5 years, and the 3-month PFS rate was 50.0% (95% confidence interval 30.0–70.0). The median PFS and overall survival were 3.1 months and 8.9 months, respectively. The response rate and disease control rate were 8.3% and 50.0%, respectively. Common grade 3/4 adverse events were acneiform rash (17%), hypomagnesemia (13%), and dry skin (13%). No treatment-related deaths occurred.

Conclusion

Irinotecan plus panitumumab rechallenge is a promising third-line treatment regimen in patients with metastatic wild-type KRAS colorectal cancer.

Clinical Trial Identification

UMIN000015916.

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Acknowledgements

The authors would like to thank the patients and their families, their collaborators who contributed to the study and recruited patients, and the members of the Japan Clinical Cancer Research Organization (JACCRO) Data Center and Support Office. The authors would also like to thank Yasuhiro Shimada, Kenji Omura, and Toru Takebayashi for the independent data and safety monitoring committee.

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Authors and Affiliations

  1. Department of Clinical Oncology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa, 761-0793, Japan

    Akihito Tsuji

  2. Aizawa Comprehensive Cancer Center, Aizawa Hospital, Matsumoto, Japan

    Masato Nakamura

  3. Department of Surgery, Japanese Red Cross Society Himeji Hospital, Himeji, Japan

    Takanori Watanabe

  4. Department of Surgery, Gastrointestinal Center, Kyoto Katsura Hospital, Kyoto, Japan

    Dai Manaka

  5. Gastroenterological Surgery, Fujita Health University, Toyoake, Japan

    Hiroshi Matsuoka

  6. Department of Surgery, Nagoya Medical Center, Nagoya, Japan

    Masato Kataoka

  7. Department of Clinical Medicine, Kitasato University School of Pharmacy, Tokyo, Japan

    Masahiro Takeuchi

  8. Division of Medical Oncology, Showa University Fujigaoka Hospital, Yokohama, Japan

    Wataru Ichikawa

  9. Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, Japan

    Masashi Fujii

Authors
  1. Akihito Tsuji
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  2. Masato Nakamura
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  8. Wataru Ichikawa
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  9. Masashi Fujii
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Corresponding author

Correspondence to Akihito Tsuji.

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Funding

This work was supported by the JACCRO and funded by Takeda Pharmaceutical Co., Ltd.

Conflicts of interest

A.T. and W.I. have received grants from Takeda Pharmaceutical Co., Ltd. M.N., T.W., D.M., H.M., M.K., M.T., and M.F. declare that they have no conflicts of interest that might be relevant to the contents of this article.

Ethics approval

This study has been reviewed and approved by the JACCRO Institutional Review Board (No.2013-7).

Consent to participate

Written, informed consent was obtained from all study participants.

Consent for publication

Not applicable.

Availability of data and material

Not applicable.

Code availability

Not applicable.

Author contributions

AT, WI, and MF analyzed and interpreted patient data and contributed significantly to the writing of the manuscript. All authors enrolled patients, treated them, participated in manuscript preparation, and read and approved the final manuscript.

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Tsuji, A., Nakamura, M., Watanabe, T. et al. Phase II Study of Third-Line Panitumumab Rechallenge in Patients with Metastatic Wild-Type KRAS Colorectal Cancer Who Obtained Clinical Benefit from First-Line Panitumumab-Based Chemotherapy: JACCRO CC-09. Targ Oncol 16, 753–760 (2021). https://doi.org/10.1007/s11523-021-00845-y

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  • DOI: https://doi.org/10.1007/s11523-021-00845-y

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