Relationships Between Köhne Category/Baseline Tumor Load and Early Tumor Shrinkage, Depth of Response, and Outcomes in Metastatic Colorectal Cancer

Andrea Sartore-Bianchi,Pilar García-Alfonso,Michael Geissler,Claus-Henning Köhne,Marc Peeters,Timothy Price,Manuel Valladares-Ayerbes,Ying Zhang,Peter Burdon,Julien Taieb,Dominik P Modest

doi:10.1016/j.clcc.2021.05.007

Abstract

BackgroundIn metastatic colorectal cancer (mCRC), there are limited data on associations between early tumor shrinkage (ETS), depth of response (DpR), and patient characteristics. MethodsData from patients with RAS wild-type mCRC who had participated in the PRIME (NCT00364013) and PEAK (NCT00819780) studies were analyzed retrospectively. ETS and DpR were assessed by baseline Köhne category/BRAF status (PRIME) and baseline tumor load (pooled PRIME and PEAK). ResultsAnalysis populations included 436 to 665 patients. Patients’ chances of achieving ETS of 30% or greater were 63.8%, 50.4%, and 41.9% in the low-, medium-, and high-risk Köhne categories, and 21.7% in those with BRAF mutations. Corresponding percentages for the highest DpR classification (71%-100%) were 47.7% (low risk), 23.6% (medium risk), 10.0% (high risk), and 4.2% (BRAF mutant). No clear relationship was observed between baseline tumor load and ETS or DpR. An ETS of 30% or greater and higher DpR values were associated with statistically significant prolongation of median progression-free survival and overall survival. ConclusionPatients with mCRC categorized at baseline by the Köhne criteria as high risk or with BRAF mutations have lower chances of achieving an ETS of 30% or greater or a high DpR. Baseline tumor load was not predictive of ETS or DpR. Favorable ETS or DpR is associated with improved progression-free and overall survival.

Highlights

The PRIME and PEAK studies, including the additional analyses presented here, were funded by Amgen (Europe) GmbH
Patients in the PEAK and PRIME studies did not have identical baseline characteristics, meaning that the pooled data used for the tumor load analysis were heterogeneous. This pooled, retrospective analysis shows that patients with metastatic colorectal cancer (mCRC) categorized at baseline by the Köhne criteria as having high risk, or having BRAF mutations, have lower chances of achieving an early tumor shrinkage (ETS) of 30% or greater or a high depth of response (DpR) when compared with low- or medium-risk patients
There were no clear trends between baseline tumor load and the likelihood of achieving an ETS of 30% or greater or a high DpR

Summary

Introduction

The PRIME and PEAK studies, including the additional analyses presented here, were funded by Amgen (Europe) GmbH. Open access for this article was funded by Amgen (Europe) GmbH. In 2018, colorectal cancer (CRC) was reported to be the third most common form of cancer and the second leading cause of cancer death.[1,2] A high proportion of cases develop into. Paris, France 11Medical Department, Division of Hematology, Oncology and Tumor Immunology, Charité University Medicine Berlin, Campus Virchow Klinikum (CVK), Berlin, Germany metastatic disease (mCRC), with a 5-year survival rate of approximately 13%.3,4. First-line treatment options for mCRC include chemotherapy, anti-vascular endothelial growth factor antibody (bevacizumab), and anti-epidermal growth factor receptor (EGFR) antibodies (panitumumab, cetuximab).[5,6,7,8] RAS mutations, which occur in 50% to 60% of patients with CRC, are predictive of Center/University of Milan (La Statale), Milan, Italy 2Department of Oncology, General Universitario Gregorio Marañón, Madrid, Spain 3Geschäftsführung, Städtisches Klinikum Karlsruhe, Karlsruhe, Germany 4Department of Oncology and Haematology, Klinikum Oldenburg, Oldenburg, Germany 5Department of Oncology, Antwerp University Hospital/Antwerp University, Edegem, Belgium 6 Haematology and Medical Oncology Unit, Queen Elizabeth Hospital/University of Adelaide, Adelaide, Australia 7Department of Medical Oncology, Hospital Universitario Reina Sofia, IMIBIC, CIBERONC, Córdoba, Spain 8 Biostatistics, Amgen Inc., Thousand Oaks, California, USA 9 European Medical, Amgen (Europe) GmbH, Rotkreuz, Switzerland 10Sorbonne Paris Cité, Paris Descartes University, Georges Pompidou European

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