Biologic Therapy in Head and Neck Cancer: A Road with Hurdles

Table 2

Targeted agents under investigation in combination with cetuximab.

Trial phase	Associated Compound	Target/mechanism of action	Disease setting	Administration	Associated treatment
Randomized phase III	With or without 0S1-906	IGF-1R/IR	R/M platinum refractory	po
	With or without E7050	VEGFR-2; c-MET	R/M platinum refractory	po
	With or without bevacizumab	VEGF	LA	iv	Pemetrexed + RT
	With or without everolimus	mTOR	LA	po	Paclitaxel + P IC
Single arm phase II	Sorafenib	CRAF; BRAF; c-KIT; FLT-3; VEGFR-2/3; PDGFR-𝛽	R/M	po
	Temsirolimus	mTOR	R/M	iv	P
	PX-866	Phosphoinositide-3-kinase	R/M	po
	Everolimus	mTOR	R/M	po	Carbo
	Bevacizumab	VEGF	R/M	iv
	Bevacizumab	VEGF	LA	iv	(TP) → RT + P
	EMD1201081	Toll-like receptor 9 agonist	R/M 2nd	sc
	Lenalidomide	Immunomodulating agent	R/M; solid tumors	po
	Dasatinib	BCR-ABL; Src; c-KIT; EPH; PDGFR𝛽	LA	po	RT (±P)
	BMS-754807	IGF-1R/IR	solid tumors	po
	Erlotinib	EGFR	R/M	po	carbo + paclitaxel
	EGFR Antisense DNA	EGFR		Intratumoral	RT
Phase l	Everolimus	mTOR	LA	po
	Lenalidomide	Immunomodulating agent	R/M	po	RT + P
	IPI-926	Smoothened, hedgehog pathway	R/M	po
	VTX-2337	Toll-like receptor 8 agonist	R/M	sc
	MM-121	ErbB3	Advanced tumors	iv	Irinotecan
	Lapatinib	EGFR/HER2	Solid tumors	po
	RO5479599*	HER-3	HER-3 +tumors	iv
	Sunitinib	PDGFR𝛼/𝛽; VEGFRl-3; KIT; FLT3; CSF-1R; RET	Local recurrence	po	RT
	Vorinostat	HDACi	LA	po	RT + P

mTOR: mammalian target of rapamycin; LA: locoregionally advanced; po: per os; iv: intravenously; RT: radiotherapy; EGFR: epidermal growth factor receptor;
P: cisplatin; carbo: carboplatin; T: docetaxel; R/M: recurrent/metastatic; OPH: oropharyngeal cancer; c-MET: hepatocyte growth factor receptor;
HDACi: histone deacetylase inhibitor; IGF-1R/IR: insulin-like growth factor-l/insulin receptor.
PDGFR𝛽: platelet-derived growth factor recpetor 𝛽; BRAF: serine/threonine-protein kinase B-Raf; c-KIT: mast/stem cell growth factor receptor.
*: RO5479599 a lone or with erlotinib or with cetuximab.