Is metastatic pancreatic cancer an untargetable malignancy?

Table 1 Phase III trials evaluating gemcitabine with a targeted therapy in advanced or metastatic pancreatic cancer

Ref.	Regimen	Mechanism of action	PFS	OS
Moore et al[7]	Gemcitabine/erlotinib	Anti-EGFR	3.7	6.2
	Gemcitabine		3.5	5.9
Philip et al[12]	Gemcitabine/cetuximab	Anti-EGFR	3.4	6.3
	Gemcitabine		3.0	5.9
Fuchs et al[17]	Gemcitabine/ganitumab	Anti-IGF1R	3.7	7.2
	Gemcitabine		3.6	7.0
IokaT et al[15]	Gemcitabine/axitinib	TKI	NA	5.1
	Gemcitabine		NA	5.4
Gonçalves et al[16]	Gemcitabine/sorafenib	TKI	5.7	9.2
	Gemcitabine		3.8	8.0
Kindler et al[13]	Gemcitabine/bevacizumab	Anti-VEGF	3.8	5.8
	Gemcitabine		2.9	5.9
Rougier et al[14]	Gemcitabine/aflibercept	Anti-VEGF	3.7	6.5
	Gemcitabine		3.7	7.8

PFS: Progression free survival; OS: Overall survival; EGFR: Epidermal growth factor receptor; IGF1R: Insulin-like growth factor receptor 1; TKI: Tyrosine kinase inhibitor; VEGF: Vascular endothelial growth factor; NA: Not available.

Table 2 Clinical trials in metastatic pancreatic cancer associating two targeted therapies to chemotherapeutical agents

Ref.	Regimen	Phase	PFS	OS
Van Cutsem et al[18]	Gemcitabine/erlotinib/bevacizumab Gemcitabine/erlotinib	III	4.6	7.1
			3.6	6.0
Philip et al[19]	Gemcitabine/erlotinib/cixutumumab Gemcitabine/erlotinib	I	3.6	7.0
			3.6	6.7
Watkins et al[20]	Gemcitabine/capecitabine/erlotinib/bevacizumab	I/II	8.4	12.6
NCT02450656 (ongoing trial)	Afatinib/selumetinib	II	NA	NA
	Capecitabine

PFS: Progression free survival; OS: Overall survival; NA: Not available.

Table 3 New treatment modalities based on targeted therapies in metastatic pancreatic cancer

Treatment modality	Mechanism of action	Target
Immunotherapy	Check point inhibitors	CTLA4
	Adoptive cell therapy	T-cells
Epigenetics	Histone acetylation	Histones
Stromal extracellular matrix	Hyaluronidase	Hyaluronan
Tumor suppressor genes regulation	miRNA inhibitors	TP53-SMAD4- CDKN2A
	Anti-PARP	BRCA1-BRCA2

CTLA4: Cytotoxic T-lymphocyte-associated antigen 4; TP53-SMAD4- CDKN2A: Tumor protein p53 - cyclin-dependent kinase inhibitor 2A; BRCA: Breast cancer; PARP: PolyADP ribose polymerase.