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.

Köhne, Claus-Henning;Karthaus, Meinolf;Mineur, Laurent;Thaler, Josef;Hofheinz, Ralf-Dieter;et.al.
(2019) Drugs in R & D — Vol. 19, n° 3, p. 267-275 (2019)

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Authors
  • Köhne, Claus-Henning
    Author
  • Karthaus, Meinolf
    Author
  • Mineur, Laurent
    Author
  • Thaler, Josef
    Author
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  • Hofheinz, Ralf-Dieter
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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.
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Köhne, C.-H., Karthaus, M., Mineur, L., Thaler, J., Van den Eynde, M., Gallego, J., Koukakis, R., Berkhout, M., & Hofheinz, R.-D. (2019). 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. Drugs in R & D, 19(3), 267-275. https://doi.org/10.1007/s40268-019-0278-8 (Original work published 2019)