Current therapeutic strategies for advanced pancreatic cancer: A review for clinicians

Table 2 Available clinical results about multitarget inhibition in pancreatic adenocarcinoma

Combination	Molecular targets	Frequence of mutation1	Setting/combination	Results
Everolimus + Erlotinib	mTOR + EGFR	+, +	Phase II, 16 patients, chemo-refractory	No responses
(Javle 2010)
Bevacizumab + Erlotinib	VEGF + EGFR	+, +	Phase III, 301 patients, plus GEM + ERLO	No increase in OS respect GEM+ ERLO
(Van Cutsem 2009)
Cixutumumab + Erlotinib	IGF-1R + EGFR	+, +	Phase Ib/II, 126 patients, plus GEM	No increase in PFS and OS respect GEM + ERLO
(Philip 2014)
Sunitinb (Bergmann 2015)	VEGFR + PDGFR	+, +	Phase II, 106 patients, 1st line, plus GEM	No increase in TTP and OS respect GEM

GEM: Gemcitabine; ERLO: Erlotinib; Nab-P: Nab-paclitaxel; OS: Overall survival; PFS: Progression-free survival; mTOR: Mammalian target of rapamycin; EGFR: Epidermal growth factor receptor; IGF-1R: Insulin-like growth factor 1 receptor; VEGFR: Vascular endothelial growth factor receptor; PDGFR: Platelet-derived growth factor receptor; TTP: Time to progression.

¹To obtain this parameter, a mean between the frequency of somatic mutations in the target was calculated from the paper by Biankin et al[108] and Waddel et al[109], Figure 1. Three parameter were possible: +++ ≥ 75%, ++ > 50%, + ≤ 50%.