Early tumour response as a survival predictor in previously- treated patients receiving triplet hepatic artery infusion and intravenous cetuximab for unresectable liver metastases from wild-type KRAS colorectal cancer

Publication date: November 2016
Source:European Journal of Cancer, Volume 68
Author(s): Mohamed Bouchahda, Valérie Boige, Denis Smith, Abdoulaye Karaboué, Michel Ducreux, Mohamed Hebbar, Céline Lepère, Christian Focan, Rosine Guimbaud, Pasquale Innominato, Sameh Awad, Carlos Carvalho, Salvatore Tumolo, Stephanie Truant, Thierry De Baere, Denis Castaing, Philippe Rougier, Jean-François Morère, Julien Taieb, René Adam, Francis Lévi
BackgroundEarly tumour shrinkage has been associated with improved survival in patients receiving cetuximab-based systemic chemotherapy for liver metastases from colorectal cancer (LM-CRC). We tested this hypothesis for previously treated LM-CRC patients receiving cetuximab (500 mg/m²) and triplet hepatic artery infusion (HAI) within European trial OPTILIV.MethodsIrinotecan (180 mg/m²), 5-fluorouracil (2800 mg/m²) and oxaliplatin (85 mg/m²) were given as chronomodulated or conventional delivery. Patients were retrospectively categorised as early responders (complete or partial RECIST response after three courses) or non-early responders (late or no response). Prognostic factors were determined using multivariate logistic or Cox regression models.ResultsResponse was assessed in 57 of 64 registered patients (89%), who had previously received one to three prior systemic chemotherapy protocols. An early response occurred at 6 weeks in 16 patients (28%; 9 men, 7 women), aged 33–76 years, with a median of 12 liver metastases (LMs) (2–50), involving five segments (1–8). Ten patients had a late response, and 31 patients had no response. Grade 3–4 fatigue selectively occurred in the non-early responders (0% versus 26%; p = 0.024). Early tumour response was jointly predicted by chronomodulation—odds ratio (OR): 6.0 (1.2–29.8; p = 0.029)—and LM diameter ≤57 mm—OR: 5.3 (1.1–25.0; p = 0.033). Early tumour response predicted for both R0-R1 liver resection—OR: 11.8 (1.4–100.2; p = 0.024) and overall survival—hazard ratio: 0.39 (0.17–0.88; p = 0.023) in multivariate analyses.ConclusionsEarly tumour response on triplet HAI and systemic cetuximab predicted for complete macroscopic liver resection and prolonged survival for LM-CRC patients within a multicenter conversion-to-resection medicosurgical strategy. Confirmation is warranted for early response on HAI to guide decision making.Protocol numbers: EUDRACT 2007-004632-24NCT00852228.



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