State of the art biological therapies in pancreatic cancer

Table 1 Principal phase III clinical trials involving targeted therapy in pancreatic cancer

Agent	Target pathway	Treatment	Setting	n	mOS (mo)	PFS (mo)	FDA approval	Ref.
Erlotinib	EGFR signaling	GEM plus erlotinib	M/LA	569	6.24 vs 5.91	3.75 vs 3.55	Yes	[5]
		vs GEM plus P			(P = 0.038)	(P = 0.004)
Cetuximab	EGFR signaling	GEM plus cetuximab	M/LA	766	6.5 vs 6	3.5 vs 3	No	[17]
		vs GEM			(P = 0.14)	(P = 0.058)
Tipifarnib	KRAS pathway	GEM plus tipifarnib	M/LA	688	6.3 vs 6	3.7 vs 3.6	No	[30]
		vs GEM			(P = 0.75)	(P = 0.72)
Ganitumab	IGFR pathway	GEM plus ganitumab (12 mg/kg or 20 mg/kg)	M	800	12 mg/kg arm	12 mg/kg arm	No	[35]
		vs GEM plus P			7.0 vs 7.2	3.7 vs 3.6
					(P = 0.494)	(P = 0.520)
					60 mg/kg arm	60 mg/kg arm
					7.1 vs 7.2	3.7 vs 3.7
					(P = 0.397)	(P = 0.403)
Bevacizumab	Angiogenesis	GEM plus bevacizumab	M/LA	602	5.7 vs 6.0	4.8 vs 4.3	No	[36]
		vs GEM plus P			(P = 0.40)	(P = 0.99)
Aflibercept	Angiogenesis	GEM plus aflibercept	M/LA	546	6.5 vs 7.8	3.7 vs 3.7	No	[38]
		vs GEM plus P			(P = 0.203)	(P = 0.864)
Axitinib	Angiogenesis	GEM plus axitinib	M/LA	632	8.5 vs 8.2	4.4 vs 4.4	No	[41]
		vs GEM plus P			(P = 0.543)	(P = 0.520)
Marimastat	Tumor stroma	GEM plus marimastat	M/LA	239	5.4 vs 5.4	3 vs 3.1	No	[75]
		vs GEM			(NA)	(NA)

GEM: Gemcitabine; P: Placebo; mOS: Median overall survival; PFS: Progression free survival; n: Number of patients enrolled; LA: Locally advanced cancer; M: Metastatic cancer; NA: Not available.

Table 2 Principal phase II clinical trials involving targeted therapy in pancreatic cancer

Agent	Target pathway	Treatment	Setting	n	Ref.
Cetuximab	EGFR signaling	GEM plus cisplatin plus cetuximab	M/LA		[16]
		vs		84
		GEM plus cisplatin
Gefitinib	EGFR signaling	GEM plus gefitinib	M/LA	57	[18]
		(single arm)
Trastuzumab	EGFR signaling	GEM plus trastuzumab	M/LA	34	[20]
		(single arm)	2+/3+ HER-2 expression
Trastuzumab	EGFR signaling	Capecitabine plus trastuzumab	M/LA	17	[21]
		(single arm)	3+ HER-2 expression or gene amplification	(212 screened)
Nimotuzumab	EGFR signaling	GEM plus nimotuzumab	M/LA	18	[23]
		(single arm)
Nimotuzumab	EGFR signaling	Nimotuzumab monotherapy	Refractory to first line standard chemotherapy M/LA	56	[24]
		(single arm)
Selumetinib	KRAS/MEK pathway	Capecitabine plus selumetinib	Refractory to first line standard chemotherapy M/LA	70	[31]
		vs Capecitabine
Trametinib	KRAS/MEK pathway	GEM plus trametinib	M/LA	160	[32]
		vs GEM plus P
Sorafenib	Angiogenesis	GEM plus sorafenib	M/LA	70	[40]
		(single arm)
RO4929097	Hedgehog signaling	RO4929097 monotherapy	Refractory to first line standard chemotherapy M	18	[57]
		(single arm)
Everolimus	mTOR pathway	Everolimus plus capecitabine	M/LA	31	[67]
		(single arm)

GEM: Gemcitabine; P: Placebo; n: Number of patients enrolled; LA: Locally advanced cancer; M: Metastatic cancer.

Table 3 Principal ongoing trials involving targeted therapy in pancreatic cancer

ClinicalTrials.gov identifier	Agent	Target	Status
NCT01728818	Afatinib	EGFR signaling	Recruiting
NCT01659502	TL-118	Angiogenesis	Not yet recruiting
NCT01621243	Necuparanib	Angiogenesis	Recruiting
NCT01088815	Vismodegib	Hedgehog signaling	Recruiting
NCT01096732	Vismodegib	Hedgehog signaling	Terminated
NCT01431794	LDE-225	Hedgehog signaling	Recruiting
NCT00515866	KU-0059436	PARP inhibitor	Completed
NCT01585805	Veliparib	PARP inhibitor	Recruiting
NCT01571024	BKM120	mTOR and PI3K/Akt pathway	Recruiting
NCT01028495	RX-0201	mTOR and PI3K/Akt pathway	Completed
NCT01337765	BEZ235 + MEK162	mTOR and PI3K/Akt pathway	Completed
NCT00560963	Everolimus	mTOR pathway	Completed
NCT00075647	Temsirolimus	mTOR pathway	Completed
NCT01839487	PEGPH20	Tumor stroma	Recruiting

EGFR: Epidermal growth factor receptor; mTOR: Mammalian target of rapamycin.