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Review
. 2015 May;7(3):153-69.
doi: 10.1177/1758834015572343.

Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review

Benoist Chibaudel  1 , Christophe Tournigand  2 , Franck Bonnetain  3 , Hubert Richa  4 , Magdalena Benetkiewicz  5 , Thierry André  6 , Aimery de Gramont  7
Affiliations
Review

Therapeutic strategy in unresectable metastatic colorectal cancer: an updated review

Benoist Chibaudel et al. Ther Adv Med Oncol. 2015 May.

Abstract

Systemic therapy is the standard care for patients with unresectable advanced colorectal cancer (CRC), but salvage surgery of metastatic disease should be considered in the case of adequate tumor shrinkage. Several drugs and combinations are now available for use in treating patients with advanced CRC, but the optimal sequence of therapy remains unknown. Moreover, the administration of antitumor therapy can be modulated by periods of maintenance or treatment breaks rather than delivered as full therapy until disease progression or unacceptable toxicity, followed by reintroduction of prior full therapy when required, before switching to other drugs. Consequently, randomized strategy trials are needed to define the optimal treatment sequences. Molecular testing for Kirsten rat sarcoma viral oncogene homolog (KRAS) and neuroblastoma RAS viral oncogene homolog (NRAS) is mandatory but not sufficient to select appropriate patients for epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) therapy.

Keywords: chemotherapy; colorectal cancer; maintenance; molecular targeted agents; strategy; treatment.

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Conflict of interest statement

Conflict of interest statement: BC has served as a consultant or in an advisory role for Roche and Sanofi. CT has served as a consultant or in an advisory role and received honoraria from Roche and Sanofi. FB has served as a consultant or in an advisory role for Roche, Nestlé, and Merck Serono, has received honoraria from Roche, Nestlé, Bristol-Myers Squibb, and Merck Serono, and has received research funding from Roche. TA has served as a consultant or in an advisory role for Amgen, Merck Serono, and Roche, and has received honoraria from Amgen, Merck Serono, and Roche. AdG has served as a consultant or in an advisory role for Roche, Sanofi, and PharmaEngine and received honoraria from Roche. MB and HR have no conflicts of interest to declare.

Figures

Figure 1.
Figure 1.
Colon cancer biology: focus on epidermal growth factor (EGF) pathway and sensitivity to epidermal growth factor receptor (EGFR) monoclonal antibodies (MoAbs). (A) Frequency of KRAS, NRAS, and BRAF tumor genes mutations in patients with advanced colorectal cancer (CRC). (B) Role of tumor biology for the estimated sensitivity to EGFR MoAbs in metastatic CRC.
Figure 2.
Figure 2.
Proportion of patients (%) with graphical overall survival (OS) superiority (green), uncertain difference (orange) and absence of superiority (red) of cetuximab over bevacizumab in the AIO FIRE-3 study (A), in the CALGB/SWOG 80405 study (B), and estimation (mean) from both (C).
Figure 3.
Figure 3.
Maintenance and treatment-free interval (TFI) trials with an oxaliplatin-based induction therapy. Abbreviations: IT, induction therapy; chemo, chemotherapy; ox, oxaliplatin, FU, fluoropyrimidine; bev, bevacizumab; cetux, cetuximab; maint., maintenance. OPTIMOX2 [Chibaudel et al. 2009]; COIN [Adams et al. 2011]; CAIRO3 [Koopman et al. 2013]; SAKK 41/06 [Koeberle et al. 2013]; AIO KRK 0207 [Arnold et al. 2014]; COIN-B [Wasan et al. 2014]; OPTIMOX1 [Tournigand et al. 2006]; DREAM [Chibaudel et al. 2014b]; ACT-1 [Johnsson et al. 2013]; NORDIC VII [Tveit et al. 2012]; MACRO-2 [Alfonso et al. 2014]; MACRO [Diaz-Rubio et al. 2012]
Figure 4.
Figure 4.
Multiline therapeutic strategies in wild-type RAS metastatic colorectal cancer (mCRC): treatment decisions from first-line to salvage treatment. Abbreviations: chemo, chemotherapy; bev, bevacizumab; ox, oxaliplatin; cetux, cetuximab; iri, irinotecan; Pmab, panitumumab; FU, fluoropyrimidine, Rx, therapy. GERCOR C97-3 [Tournigand et al. 2004]; NO16966 [Saltz et al. 2008]; OPTIMOX1 [Tournigand et al. 2006]; OPTIMOX2 [Chibaudel et al. 2009]; AVF2107g [Hurwitz et al. 2004]; PRIME [Douillard et al. 2010]; CRYSTAL [Van Cutsem et al. 2009]; TML [Bennouna et al. 2013]; 181 [Peeters et al. 2010]; EPIC [Sobrero et al. 2008]; ECOG 3200 [Giantonio et al. 2007]; VELOUR [Van Cutsem et al. 2011]; BOND [Cunningham et al. 2004]; 408 [Van Cutsem et al. 2007]; CORRECT [Grothey et al. 2013]
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