Phase 2 study of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type metastatic colorectal cancer: JACCRO CC-08

Toshiki Masuishi,Hiroaki Tanioka,Hideto Fujita,Masahito Kotaka,Takeshi Suto,Dai Manaka,Tsuyoshi Takahashi ,Hiroki Hara,Tamotsu Sagawa,Ken Shimada,Wataru Ichikawa,Akinori Takagane,Masato Nakamura,Akihito Tsuji,Tadamichi Denda,Yuji Negoro,Yoshihiko Segawa,Masahiro Takeuchi,Mitsugu Kochi,Takanori Watanabe,Masashi Fujii

doi:10.1038/s41416-020-01042-w

Abstract

BackgroundRegorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC).MethodsThis Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who achieved clinical benefit with first-line cetuximab-containing therapy. The primary endpoint was 3-month progression-free survival (PFS) rate. A sample size was calculated; 30 patients with a 3-month PFS rate of 45% deemed promising and 15% unacceptable. Patients with greater and less than the cut-off value of cetuximab-free intervals (CFIs) were classified into the long and short CFI groups, respectively, in subgroup analyses.ResultsAmong 34 eligible patients who received treatment at least once, 3-month PFS rate was 44.1% (95% confidence interval, 27.4–60.8%). The median PFS and overall survival (OS) were 2.4 and 8.2 months, respectively. The response and disease control rates were 2.9 and 55.9%, respectively. PFS and OS were significantly longer in the long- than in the short CFI group.ConclusionsIrinotecan plus cetuximab rechallenge as third-line treatment for KRAS wild-type mCRC was safe and had promising activity, especially in those with a long CFI, warranting further investigation in a Phase 3 randomised trial.Clinical trial registrationUMIN000010638

Highlights

Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer
Patient characteristics The study included 36 patients enrolled between May 2013 and October 2015
One patient proved to be ineligible after initiation of protocol treatment because no blood evaluation had been performed for this patient before study enrolment

Summary

Introduction

Regorafenib or trifluridine/tipiracil as third-line treatment have limited efficacy in metastatic colorectal cancer (mCRC). METHODS: This Phase 2 trial evaluated the efficacy and safety of irinotecan plus cetuximab rechallenge as third-line treatment in KRAS wild-type mCRC patients who achieved clinical benefit with first-line cetuximab-containing therapy. The primary endpoint was 3-month progression-free survival (PFS) rate. A sample size was calculated; 30 patients with a 3-month PFS rate of 45% deemed promising and 15% unacceptable. Patients with greater and less than the cut-off value of cetuximab-free intervals (CFIs) were classified into the long and short CFI groups, respectively, in subgroup analyses. RESULTS: Among 34 eligible patients who received treatment at least once, 3-month PFS rate was 44.1% (95% confidence interval, 27.4–60.8%). CONCLUSIONS: Irinotecan plus cetuximab rechallenge as third-line treatment for KRAS wild-type mCRC was safe and had promising activity, especially in those with a long CFI, warranting further investigation in a Phase 3 randomised trial.

Methods

Results

Conclusion