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

Table 1 Ongoing clinical trials about locoregional treatments in locally advanced pancreatic cancer

Combination	Inclusion criteria	Start	Clinical trial identifier1	Expected end of accrual
FOLFIRINOX + SBRT	T ≤ 7 cm, non-metastatic	November 14	NCT02292745	November 20
RFA	Unresectable, also metastatic	June 14	NCT02166190	June 16
Cryoablation	Borderline resectable/locally advanced	November 14	NCT02336672	November 16
Radioembolization	unresectable/failure of celiac alcholization	Not available	NCT01786850	Not available
Irreversible electroporation (PAN.FIRE)	T < 5 cm, non-metastatic	September 13	NCT01939665	June 16

RFA: Radiofrequency ablation; SBRT: Stereotactic body radiation therapy;

¹Data Available from: URL: http// http://www.clinicaltrials.gov (last access 2015 May 24).

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%.

Table 3 Ongoing clinical trials about multitarget inhibition in pancreatic adenocarcinoma

Combination	Target	Frequence of mutation1	Setting	Clinical trial identifier2	Expected end of accrual
Dovitinib	FGRFR + PDGFR + VEGFR	+, +, +	Phase II, + GEM and CAPE	NCT01497392	Sep-16
Trastuzumab + Erlotinib	EGFR2 + EGFR	+, +	Phase II, + GEM	NCT01204372	Apr-15
MEK162 + Ganitumab	MEK1 + IGF-1R	+, +	Phase II, multi-disease, chemorefractory	NCT01562899	Apr-15

GEM: Gemcitabine; MEK 1: Mitogen-activated extracellular signal regulated kinase 1; CAPE: Capecitabine.

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%;

²Data Available from: URL: http// http://www.clinicaltrials.gov (last access 2015 May 24).

Table 4 Available and ongoing clinical results about drugs targeting mainly stroma in pancreatic adenocarcinoma

Combination	Target (s)	Setting	Clinical trial identifier1	Expected end of accrual
Demcizumab	Cancer stem cells by DLL4 inhibition	Phase Ib, plus GEM +/- Nab-P	NCT01189929	Concluded. presented at ASCO 2014: Increase in ORR, cardiovascular toxicity
(Gracian 2014)
Ruxolitinib (Hurwitz 2014)	Inflammation by JAK/STAT inhibition	Phase II, 2nd line, plus CAPE	NCT01423604	Concluded. presented at ASCO 2014: Benefit in patients with elevated CRP
PEGPH20	HA by Pegylated-hyaluronidase	Phase II, 1st line, plus GEM	NCT01453153	Concluded. presented at ASCO 2013: ORR 33%, especially in patients with high HA expression
(Hingorani 2013)S
‘’	‘’	Phase II, plus GEM + Nab-P	NCT01839487	July 16

CAPE: Capecitabine; CRP: C-reactive protein; GEM: Gemcitabine; HA: Hyaluronic acid; ORR: Objective response rate; DLL4: Delta like ligand 4; ASCO: American society of clinical oncology; JAK/STAT: Janus kinase/signal transducer and activator of transcription; Nab-P: Nab-paclitaxel.

¹Data Available from: URL: http// http://www.clinicaltrials.gov (last access 2015 May 24).