Sorafenib and irinotecan (NEXIRI) as second- or later-line treatment for patients with metastatic colorectal cancer and KRAS-mutated tumours: a multicentre Phase I/II trial

E Samalin, O Bouché, S Thézenas, E Francois, A Adenis, J Bennouna, J Taieb, F Desseigne, J F Seitz, T Conroy, M P Galais, E Assenat, E Crapez, S Poujol, F Bibeau, F Boissière, P Laurent-Puig, M Ychou, T Mazard, E Samalin, O Bouché, S Thézenas, E Francois, A Adenis, J Bennouna, J Taieb, F Desseigne, J F Seitz, T Conroy, M P Galais, E Assenat, E Crapez, S Poujol, F Bibeau, F Boissière, P Laurent-Puig, M Ychou, T Mazard

Abstract

Background: This trial evaluated the feasibility and efficacy of combined sorafenib and irinotecan (NEXIRI) as second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer (mCRC), who had progressed after irinotecan-based chemotherapy.

Methods: In Phase I, in a 3+3 dose escalation schedule, patients received irinotecan (125, 150 or 180 mg m(-2) every 2 weeks), in combination with 400 mg sorafenib b.d. The primary end point was the maximum-tolerated dose of irinotecan. In Phase II, the primary end point was disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS) and toxicity.

Results: Phase I included 10 patients (median age 63 (49-73)); no dose-limiting toxicity was seen. In Phase II, 54 patients (median age 60 (43-80) years) received irinotecan 180 mg m(-)(2) every 2 weeks with sorafenib 400 mg b.d. Nine patients (17%) remained on full-dose sorafenib. The DCR was 64.9% (95% CI, 51-77). Median PFS and OS were 3.7 (95% CI, 3.2-4.7) and 8.0 (95% CI, 4.8-9.7) months, respectively. Toxicities included Grade 3 diarrhoea (37%), neutropenia (18%), hand-foot syndrome (13%) and Grade 4 neutropenia (17%).

Conclusion: The NEXIRI regimen showed promising activity as second- or later-line treatment in this heavily pretreated mCRC population (ClinicalTrials.gov NCT00989469).

Figures

Figure 1
Figure 1
Trial flowchart.
Figure 2
Figure 2
Kaplan–Meier curves of (A) progression-free survival and (B) overall survival.

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