Genotype–phenotype map and molecular networks: a promising solution in overcoming colorectal cancer resistance to targeted treatment

Figures & data

Table 1. Phase III randomized controlled trials testing the efficacy and safety of cetuximab or panitumab added to chemotherapy alone or plus bevacizumab in metastatic colorectal cancer.

All patients					KRAS status				Ref.
Study	Patients (n)	Chemotherapy ± cetuximab or panitumumab	OS		PFS (HR, 95% [CI])		OS (HR, 95% [CI])
					Wild-type KRAS	Mutant KRAS	Wild-typeKRAS	MutantKRAS
CRYSTAL trial	1198	599 vs 599	NS		0.68 (0.50–0.94) (p = 0.02)	1.07 (0.71–1.61) (p = 0.75)	0.84 (0.64–1.11)	1.03 (0.74–1.44)	[13]
Tol CAIRO2 trial	736	368 vs 368	NS		No HR (p = 0.3)	No HR (p = 0.003)	No HR (p = 0.64)	No HR (p = 0.03)	[14]
Karapetis AGITG CO.17 trial	572	285 vs 287	NS		0.40 (0.30–0.54) (p < 0.001)	0.99 (0.73–1.35) (p = 0.96)	0.55 (0.41–0.74) (P<0.001)	0.98 (0.70–1.37) (p = 0.89)	[15]
Hecht^1	823	413 vs410	NS		1.36 (1.04–1.77)	1.25 (0.91–1.71)	1.89 (1.30–2.75)	1.02 (0.67–1.54)	[16]
Hecht^2	230	115 vs 115	NS		1.5 (0.82–2.76)	1.19 (0.65–2.21)	1.28 (0.50–3.25)	2.14 (0.82–5.59)	[16]
Bokemeyer OPUS trial	337	169 vs 168	NA		0.57 (0.358–0.907) (p = 0.016)	1.83 (1.095–3.056) (p = 0.019)	NA	NA	[17]

AGITG CO.17 Trial: Cetuximab vs best supportive care; CAIRO2 trial: Capecitabine + oxaliplatin+ bevacizumab ± cetuximab; CRYSTAL trial: FOLFIR ± cetuximab; Hecht¹: FOLFOX -4 + bevacizumab ± panitumumab; Hecht²: FOLFIR + bevacizumab ± panitumumab; OPUS trial: FOLFOX -4 ± cetuximab.

5-FU: Fluorouracil; Ab: Antibody; AGITG CO.17 Trial: Australasian Gastro-Intestinal Trials Group; CAIRO2 trial: Capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer; CRYSTAL trial: Cetuximab Combined with Irinotecan in First-Line Therapy for Metastatic Colorectal Cancer; FOLFIR: Folinic acid (leucovorin), 5-FU, irinotecan (Campostar); FOLFOX: Folinic acid (leucovorin), 5-FU, oxaliplatin; HR: Hazard ratio; NA: Not available; NE: Not estimated; OPUS trial: Oxaliplatin and Cetuximab in the First-Line Treatment of Metastatic Colorectal Cancer; OS: Overall survival; PFS: Progression-free survival.

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Hecht JR, Mitchell E, Chidiac T et al. A randomized Phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer. J. Clin. Oncol.27(5), 672–680 (2009).

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Bokemeyer C, Bondarenko I, Makhson A et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J. Clin. Oncol.27(5), 663–671 (2009).

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