Current situation of Panitumumab, Matuzumab, Nimotuzumab and Zalutumumab

Figures & data

Table I.  EGFR overexpression

Tumour	EGFR Overexpression (%)
Squamous cell head and neck cancer [3–5]	80–100
Colorectal cancer [6]	70–90
Non-small cell lung cancer [7]	40–80
Gastric cancer [8,9]	20–80
Pancreatic cancer [10]	30–90
Breast cancer [11]	15–90
Ovarian cancer [12]	35–70
Renal cancer [13]	50–90
Gliomas [14,15]	40–50
Prostatic cancer [16]	40–80
Cervical cancer [17]	80–100

Table II.  Main anti-EGFR monoclonal antibodies under clinical development.

	Chimeric (30% murine)	Humanized (10% murine)	Completely human (100% human)
IgG1 (ADCC)	CETUXIMAB (C-225) (Erbitux)	MATUZUMAB (EMD72000)	ZALUTUMUMAB (HuMax^TM-EGFr)
		NIMOTUZUMAB (h-R3)
IgG2 (No ADCC)			PANITUMUMAB (ABX-EGF)

ADCC: Antibody dependent cell cytotoxicity.

Table III.  Anti- EGFR monoclonal antibodies: Clinical development.

Antibody	Tumour	Study phase
Cetuximab (C-225) (Erbitux)
Chimeric IgG1	Colorectal  – Advanced	III
	– Adjuvant colon	III
	- Rectal (Pre/post-op.)	III
	Head and neck  – Advanced	III
	– Loc. advanced.(+RT)	III
	Non-small cell lung	III
	Esophagus	II
	Gastric	II
	Pancreas	III
Panitumumab (ABX-EGF) Completely human IgG2	Colorectal	III
	Non-small cell lung	II
	Head and neck	II
Matuzumab (EMD72000) Humanized IgG1	Ovarian	II
	Cervix	II
	Gastric	II
	Non-small cell lung	II
Nimotuzumab (h-R3) Humanized IgG1	Head and neck	III
	Malignant gliomas	III
Zalutumumab(HuMax^TM-EGFr) Completely human IgG1	Head-neck   – Advanced	III
	– Loc. advanced (+RT)	I/II
IMC-11F8		I
RadioThera CIM		I

Table IV.  Biomarkers for anti EGFR monoclonal antibodies in advanced colorectal cancer.

Study Treatment N of pts	EGFR gene copies FISH/CISH	K-Ras mutations	Other	No predictive value
Moroni [57] Cetuxi/panitu 31 pts	FISH +:−30% of pts RR: 89% (vs 5%) p: 0.0001	K-Ras mutated:−32% of pts RR: 20% (vs 38%) p: 0.42		Mutations in EGFR B − RAF PI3K
Sartore-Bianchi [58] Panitu 58 pts	FISH +:−38% of pts RR: 30% (vs 0%) p: 0.0009 TTP: 3.4m (vs 1.6m) p: 0.03
Lièvre [59] Cetuxi +/− irino 30 pts	CISH +:−10% of pts RR: 100% (vs 30%) p: 0.04	K-Ras mutated:−43% of pts RR: 0% (vs 65%) p < 0.0001 Sv: 6.9m (vs 16.3m) p: 0.016		Mutations in B-RAF PI3K
Romagnani [60] Cetuxi +chemoth. 27 pts	FISH +:−11% of pts RR: 42% (vs 0%) p < 0.05	K-Ras mutated:−37% of pts RR: 10% (vs 53%) p < 0.05	pTEN (IHC) -:−38% of pts RR: 0% (vs 62%) p < 0.05
Personeni [61] Cetuxi +/− irino 54 pts	FISH +:−10% of pts RR + SD: 63% (vs 33%) p< 0.05	K-Ras mutated:−24% of pts RR: 0% (vs 34%) p: 0.04		Mutations in B-RAF HER 2 (FISH)
Finocchiaro [62] Cetuxi +/− irino 85 pts	FISH +:−48% of pts
RR: 29% (vs 6%) p: 0.007 TTP: 6.6m (vs 3.7m) p: 0.05 Sv:11.3m (vs8.5m) p: 0.7	K-Ras mutated:−39% of pts RR: 6% (vs 26%) p: 0.02 TTP: 3.7m (vs 6.3m) p: 0.07 Sv: 8.3m (vs 10.8m) p: 0.2	HER 2 (FISH) +:−23% of pts RR: 15% (vs 19%) p: 1 TTP: 3.7m (vs 5.8m) p: 0.01 Sv: 6.6m (vs 11.3m) p: 0.03	EGFR (IHC)
Khambata-F [63] Cetuxi 110 pts		K-Ras mutated:−37% of pts RR + SD: 10% (vs 48%) p: 0.0003 TTP: 3.7m (vs 6.3m) p: 0.07 Sv: 8.3m (vs 10.8m) p: 0.2	Epiregulin* (high expression): −50% of pts TTP: 3.4m (vs1.9m) p: 0.0001 Amphiregulin* (high expression) −50% of pts TTP: 3.8m (vs1.9m) p: 0.0001
De Roock [64] Cetuxi + /− irino 37 pts		K-Ras mutated:−46% of pts RR: 0% (vs 40%) p: <0.05

Cetuxi: cetuximab; Panitu: panitumumab; irino: irinotecan; chemoth.: chemotherapy; RR: response rate; SD: stable disease; TTP: time to tumour progression; Sv: survival; IHC: inmunohistochemistry * Tumor mRNA levels.