Table 3.

Tumor epidermal growth factor receptor gene copy number and outcome of panitumumab- or cetuximab-based treatment in patients with metastatic colorectal cancer^*

First author (reference)	Treatment [type of study; type of patients]	No of patients with increased GCN/total No. of patients (%) [cutoff†; methodology]	Outcome by GCN status, No. of patients (%)‡						Association of increased EGFR GCN with response and survival parameters
			Complete or partial response		Stable disease		Progressive disease
			Increased	Normal	Increased	Normal	Increased	Normal
Monotherapy
Sartore-Bianchi (94)	Panitumumab [patient cohort, chemotherapy refractory]	20/58 (34) [≥2.47; FISH]	6/20 (30)	0/38 (0)	5 (25)	9 (24)	9 (45)	29 (76)	No OR if mean EGFR GCN of <2.47 copies per nucleus or <43% of tumor cells with chromosome 7 polysomy vs 6/20 (30%; P < .001) and 6/19 (32%; P < .001) among those with higher values. Mean EGFR GCN of <2.5 copies per nucleus or <40% of tumor cells with chromosome 7 polysomy associated with shorter PFS (P =.0153 and .0386, respectively) and OS (P = .0145 and .0290, respectively)
Other
Cappuzzo (95)	Cetuximab ± CT [patient cohort, chemotherapy refractory]	43/85 (51) [2.92; FISH]	14/43 (33)	1/42 (2)	NA	NA	NA	NA	Increased EGFR GCN associated with higher OR (P < .001) and longer TTP (6.6 vs 3.5 mo, P = .02)
Personeni (96)	Cetuximab ± CT [patient cohort, chemotherapy refractory]	[≥2.83; FISH]	NA	NA	NA	NA	NA	NA	Longer PFS (5.5 vs 4.0 mo, P = .25) and OS (10 vs 8.3 mo, P = .037) in patients with mean GCN ≥2.83
Frattini (58)	Cetuximab ± CT [patient cohort, chemotherapy naïve and refractory]	8/27(30) [≥3 EGFR/ CEP7; FISH] or 16/27 (59) [≥4.00 EGFR]	6/8 (75) or 4/16 (25)	0/3 (0)	0/8 (0) or 2/16(12)	1/3 (33)	2/8 (25) or 10/16 (62)	2/3 (67)	Two patients with increased EGFR GCN had PD, possibly due to concomitant KRAS mutations. All NR with EGFR gene amplification or increased GCN also showed concomitant KRAS mutations and/or absent PTEN expression
Lievre (34)	Cetuximab ± CT [patient cohort, chemotherapy naïve and refractory]	3/30 (10)] [≥6; CISH]§	3/3 (100)	8/27 (30)	0 (0)	6 (22)	0 (0)	13 (48)	Increased EGFR GCN in 27% of OR vs 0% of NR (P = .04)
Moroni (26)	Panitumumab or cetuximab ± CT [patient cohort, chemotherapy naïve and refractory]	9/29 (31) [≥3; FISH]	8/9‖ (89)	1/20 (5)	0 (0)	5 (25)	1(11)	14 (70)	Increased EGFR GCN in 8/9 (89%) OR vs 1/20 (5%) NR (P < .001)

^*CEP7 = chromosome 7 control; CISH = chromogenic in situ hybridization; CT = chemotherapy; EGFR = epidermal growth factor receptor; FISH = fluorescence in situ hybridization; GCN = gene copy number; NA = data not available; NR = nonresponders; OR = objective response or responder (ie, complete or partial response); OS = overall survival; PD = progressive disease; PFS = progression-free interval; PTEN = phosphatases and tensin homolog; TTP = time to disease progression.

^†Expressed as number per nucleus.

^‡Expressed as a percentage of patients with increased or normal GCN (the denominator is also shown in the first two columns).

^§In more than 50% of cancer cells or presence of large gene copy cluster.

^‖High overall response rate in this study was due to a clinical enrichment strategy.