Predicting cetuximab efficacy in patients with advanced colorectal cancer

Figures & data

Table 1 EGFR GCN by FISH as a biomarker of cetuximab sensitivity

Study	Number of patients	Treatment	Method	Endpoint Response rate/ time to progression
Moroni et al^Citation26	31	Cetuximab or panitumumab	EGFR GCN FISH	ORR
Cappuzzo et al^Citation27	85	Cetuximab	increased EGFR (>2.92 EGFR gene copies per cell) by FISH	ORR TTP
Italiano et al^Citation28	47	Cetuximab plus chemotherapy	EGFR GCN FISH	ORR PFS OS
Sartore-Bianchi et al^Citation29		Phase III panitumumab versus best supportive care	EGFR GCN <2.5/nucleus <40% cells displaying Chromosome 7 polysomy (associated with inferior outcome)	PFS OS PFS OS
Personeni et al^Citation30	87	Cetuximab ± irinotecan	Increased mean EGFR GCN FISH	PFS OS
Khambata-Ford et al^Citation31	80	Cetuximab	EGFR GCN by PCR increased	DCR
Laurent-Puig et al^Citation32	173	Cetuximab	EGFR polysomy or amplification	PFS

Abbreviations: DCR, disease control rate; EGFR, epidermal growth factor receptor; FISH, fluorescent in situ hybridization; GCN, gene copy number; ORR, overall response rate; OS, overall survival; PCR, polymerase chain reaction; PFS progression-free survival; TTP, time to progression.

Table 2 Studies demonstrating tumor KRAS mutation as a negative predictor of anti-EGFR response

Study	Number	Agent	WT:MT	ORR, MT:WT (%)
Lievre et al^Citation37	76	Cetuximab plus chemotherapy	49:27	0 (0%):24 (49%)
De Roock et al^Citation38	113	Cetuximab Chemotherapy + cetuximab	67:46	0 (0%):27 (41%)
Khambata-Ford et al^Citation31	80	Cetuximab	50:30
Amado et al^Citation39	427	Panitumumab	243:184	0 (0%):31 (17%)
Tol et al^Citation40 (CAIRO-2)	582	CapeOx + bev CapeOx + bev + cetuximab	156:108 158:98	78 (50%):64 (59.2%) 97 (61.4%):45 (45.9%)
Van Cutsem et al^Citation41 (CRYSTAL)	540	FOLFIRI FOLFIRI + cetuximab	176:87 172:105	76 (43.2%):35 (40.2%) 102 (59.3%):38 (36.2%)
Bokemeyer et al^Citation42 (OPUS)	315	FOLFOX-4 FOLFOX + cetuximab	97:59 82:77	33 (34%):31 (52%) 47 (57%):26 (33%)
Tveit et al^Citation43 (NORDIC FLOX)	566	FLOX FLOX + cetuximab FLOX + cetuximab (intermittent)	48:28 54:40 55:32	46 (47%):23 (30%) 45 (46%):35 (37%) 56 (64%):27 (31%)
Maughan et al^Citation44 (MRC COIN)	1,316	FOLFOX/CapeOx FOLFOX/CapeOx + cetuximab	245:169 362:297	209 (57%):not available 232 (64%):not available

Abbreviations: bev, bevacizumab; CapeOx, capecitabine plus oxaliplatin; EGFR, epidermal growth factor receptor; FLOX, 5-fluorouracil, folinic acid, oxaliplatin; FOLFIRI, folinic acid, 5-fluorouracil, and irinotecan; FOLFOX, oxaliplatin, folinic acid, and 5-fluorouracil; ORR, overall response rate; MT, mutant; WT, wild type.

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