Impact of Primary Tumour Location and Early Tumour Shrinkage on Outcomes in Patients with RAS Wild-Type Metastatic Colorectal Cancer Following First-Line FOLFIRI Plus Panitumumab

Claus-Henning Köhne, Meinolf Karthaus, Laurent Mineur, Josef Thaler, Marc Van den Eynde, Javier Gallego, Reija Koukakis, Marloes Berkhout, Ralf-Dieter Hofheinz, Claus-Henning Köhne, Meinolf Karthaus, Laurent Mineur, Josef Thaler, Marc Van den Eynde, Javier Gallego, Reija Koukakis, Marloes Berkhout, Ralf-Dieter Hofheinz

Abstract

Objective: Data from a trial of first-line panitumumab plus FOLFIRI (folinic acid, infusional 5-fluorouracil and irinotecan) in metastatic colorectal cancer were retrospectively analysed to investigate the effects of primary tumour location and early tumour shrinkage on outcomes.

Methods: Patients with RAS wild-type metastatic colorectal cancer from a single-arm, open-label phase II study (NCT00508404) were included. Tumours located from the splenic flexure to rectum and in the caecum to transverse colon were defined as left- and right-sided, respectively. Baseline characteristics were summarised by primary tumour location and the effects of primary tumour location on outcomes-including objective response rate, resection rate, depth of response, duration of response and progression-free survival-were analysed. Progression-free survival and objective response rate were analysed by early tumour shrinkage status.

Results: Primary tumour location was determined in 52/69 (75%) patients with RAS wild-type metastatic colorectal cancer; 45 (87%) had left-sided disease. Median progression-free survival was longer in patients with left-sided tumours (11.2 vs. 7.2 months for right-sided disease) and more of these patients experienced early tumour shrinkage ≥ 30% (53% vs. 29%). Early tumour shrinkage ≥ 30% was associated with improved progression-free survival irrespective of tumour location. More patients with early tumour shrinkage ≥ 30% achieved a partial or complete response. Objective response rate, duration of response, depth of response and resection rates were similar in patients with left- and right-sided tumours.

Conclusions: This analysis has confirmed a prognostic effect of primary tumour location in patients with RAS wild-type metastatic colorectal cancer receiving first-line panitumumab plus FOLFIRI. Early tumour shrinkage was associated with improved progression-free survival irrespective of tumour location. In right-sided disease, early tumour shrinkage may identify a subgroup of patients who might respond to panitumumab. CLINICALTRIALS.

Gov identifier: NCT00508404.

Conflict of interest statement

Claus-Henning Köhne has received honoraria from Amgen, Bayer, Merck, Pfizer and Servier. Meinolf Karthaus has consulting/advisory roles and has participated in steering committees for Amgen and has received travel/accommodation/expenses from Amgen. Laurent Mineur has consulting/advisory roles for Bayer and Merck, and has received travel/accommodation/expenses from Merck and Ipsen, honoraria from Amgen, Bayer, Ipsen, Merck and Sanofi, and research funding from Chugai, Merck and Sanofi. Josef Thaler has received honoraria and research funding from Amgen. Marc Van den Eynde has consulting/advisory roles for Amgen, Bayer, Merck and Servier, and has received travel/accommodation/expenses from Amgen, Bayer, Merck and Roche, honoraria from Amgen, Bayer, Merck, Roche, Sanofi and Servier, and research funding from Roche. Javier Gallego has consulting/advisory roles for Amgen, Bayer, Celgene, Lilly, Merck Serono, Roche and Sanofi. Reija Koukakis is an Amgen Ltd. employee and owns restricted shares in Amgen. Marloes Berkhout is an Amgen (Europe) GmbH employee and owns restricted shares in Amgen. Ralf-Dieter Hofheinz has received honoraria (lecturer fees) and clinical trial funding from Amgen Ltd. and Merck.

Figures

Fig. 1
Fig. 1
Impact of primary tumour location on progression-free survival (PFS)
Fig. 2
Fig. 2
Impact of early tumour shrinkage (ETS) on progression-free survival (PFS)
Fig. 3
Fig. 3
Impact of early tumour shrinkage (ETS) on objective response rate: waterfall plot of relative changes in maximum tumour diameter after 8 weeks of treatment, ETS and characterisation of best objective response (n = 65). Response evaluation according to modified Response Evaluation Criteria in Solid Tumors version 1 (mRECIST v.1). CR complete response, PD progressive disease, PR partial response, SD stable disease

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