Relation of cetuximab-induced skin toxicity and early tumor shrinkage in metastatic colorectal cancer patients: results of the randomized phase 3 trial FIRE-3 (AIO KRK0306)

Holch, J. W.; Held, S.; Stintzing, S.; Fischer von Weikersthal, L.; Decker, T.; Kiani, A.; Kaiser, F.; Heintges, T.; Kahl, C.; Kullmann, F.; Scheithauer, W.; Moehler, M.; Einem, J. C. von; Michl, M. und Heinemann, V (2020): Relation of cetuximab-induced skin toxicity and early tumor shrinkage in metastatic colorectal cancer patients: results of the randomized phase 3 trial FIRE-3 (AIO KRK0306). In: Annals of Oncology, Bd. 31, Nr. 1: S. 72-78

Abstract

Background: Cetuximab-induced skin toxicity (Cet-ST) is positively associated with outcome in metastatic colorectal cancer (mCRC). Besides its predictive relevance for targeted therapy, we investigated its prognostic impact with early tumor shrinkage (ETS) >= 20%, another on-treatment surrogate for clinical outcome in FIRE-3. Patients and methods: FIRE-3 evaluated first-line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab (FOLFIRI/Cet) versus FOLFIRI plus bevacizumab (FOLFIRI/Bev) in mCRC patients with RAS-WT tumors (i.e. wild-type in KRAS and NRAS exons 2-4). Retrospective data on Cet-ST that occurred during cycles 1-3 of treatment were correlated with efficacy endpoints, including ETS. To control for guarantee-time bias, only patients who had completed three or more treatment cycles were considered. Results: Of 199 patients treated with FOLFIRI/Cet, 181 (91.0%) completed three or more treatment cycles. A significant survival benefit of FOLFIRI/Cet over FOLFIRI/Bev was only evident in patients developing Cet-ST grade 2-3 [41.0 versus 26.6 months;hazard ratio (HR) = 0.73;95% confidence interval (CI): 0.61-0.87;P < 0.001] compared with Cet-ST grade 0-1 (HR = 0.90;95% CI: 0.67-1.20;P = 0.48). Regarding prognosis, Cet-ST grade 2-3 (n = 75;41.4%), compared with Cet-ST grade 0-1 (n = 106;58.6%), was associated with prolonged overall survival (OS;HR = 0.62;95% CI: 0.42-0.91;P = 0.01). In multivariate analysis, both Cet-ST (HR = 0.66;95% CI: 0.50-0.87;P = 0.003) and ETS (HR = 0.55;95% CI: 0.41-0.74;P < 0.0001) were independently prognostic for OS. Absence of both Cet-ST grade >= 2 and ETS identified a subgroup of patients with very poor prognosis (median OS 15.1 months). Conclusions: In FIRE-3, the addition of cetuximab to FOLFIRI was associated with superior OS compared with FOLFIRI/Bev only in patients developing Cet-ST grade >= 2. Regarding prognostic relevance, both Cet-ST and ETS were independent and early predictors of survival. The present analysis supports that a combined evaluation of on-treatment parameters such as Cet-ST and ETS may help to guide treatment of mCRC.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0923-7534
• Sprache: Englisch