Early metabolic response in sequential FDG-PET/CT under cetuximab is a predictive marker for clinical response in first-line metastatic colorectal cancer patients: results of the phase II REMOTUX trial

Anne Katrin Berger,Dirk Jäger,Claudia Trierweiler,Leonidas Apostolidis,Uwe Haberkorn,Tim Frederik Weber,Stephan Lücke,Florian Lordick,Carl Von Gall,Jennifer Ose,Angelika Freitag,Mareike Dietrich,Ulrich Abel,Annika Stange,Carsten Grüllich,Georg Martin Haag,Frederik Giesel

doi:10.1038/s41416-018-0152-4

Abstract

BackgroundTo assess the predictive value of early metabolic response (ΔSUV) after short-term treatment with first-line cetuximab in patients (pts) with RAS-wt metastatic colorectal cancer (mCRC).MethodsIn this prospective phase II study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2 weeks. ΔSUV was assessed with FDG-PET/CT on days 0 and 14. Early clinical response (ECR) was evaluated with CT on day 56 after treatment with FOLFIRI-cetuximab. Primary endpoint was the predictive significance of ΔSUV for ECR. Secondary endpoints were PFS (progression free survival), OS and the influence of ΔSUV on survival.ResultsForty pts were enroled and 33 pts were evaluable for the primary endpoint. The CT response rate was 57.6%. For responders, ΔSUV was significantly higher (p = 0.0092). A significant association of ΔSUV with ECR was found (p = 0.02). Median PFS was 11.7 months and median OS was 33.5 months with a 1-year survival rate of 87.9%. ΔSUV was found to significantly impact the hazard for OS (p = 0.045).ConclusionsWe demonstrate that cetuximab induces metabolic responses in mCRC pts. The study endpoint was met with the ΔSUV discriminating between responders and non-responders. However, these data should be validated in larger patient cohorts.

Highlights

The median overall survival (OS) for patients with metastasised colorectal cancer is almost 2.5 years with response rates of 60% for the most active regimen.[1]
Recruitment and patient characteristics From February 2011 to November 2014, 40 patients were enroled at our centre
Despite our rather small sample size, we found that ΔSUV had a significant impact on OS, suggesting that early metabolic response may hold prognostic value beyond prediction of early clinical response

Summary

Introduction

The median overall survival (OS) for patients with metastasised colorectal cancer (mCRC) is almost 2.5 years with response rates of 60% for the most active regimen.[1]. We conducted a prospective phase II trial with sequential FDGPET/CT before and after a 2-week run-in phase with single-agent cetuximab in RAS-wt first-line mCRC patients. We aimed to evaluate the predictive significance of early changes in FDG uptake under single-agent cetuximab for the first morphological response as measured on day 56 under treatment with the FOLFIRI-cetuximab regimen. To assess the predictive value of early metabolic response (ΔSUV) after short-term treatment with first-line cetuximab in patients (pts) with RAS-wt metastatic colorectal cancer (mCRC). METHODS: In this prospective phase II study, RAS-wt mCRC pts received a single-agent cetuximab run-in therapy of 2 weeks. Clinical response (ECR) was evaluated with CT on day 56 after treatment with FOLFIRI-cetuximab. The study endpoint was met with the ΔSUV discriminating between responders and non-responders These data should be validated in larger patient cohorts

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