Emerging treatments for advanced pancreatic cancer: clinical potential of albumin-bound paclitaxel

Figures & data

Table 1 Main Phase III studies comparing combination chemotherapy versus single-agent gemcitabine in advanced pancreatic cancer

Reference	n	Patient population	Treatment arms	Primary endpoint	Response rate (%)	Disease control (%)	Median PFS (months)	Median OS (months)
Louvet et al^Citation57	313	Locally advanced or metastatic	Gemcitabine	OS	17.3	26.9	3.7	6.9
			Gemcitabine–oxaliplatin		26.8	38.2	5.8	8.8
					(P=0.04)	(P=0.03)	HR 0.75 (P=0.04)	HR 0.82 (P=0.13)
Heinemann et al^Citation58	195	Locally advanced or metastatic	Gemcitabine	OS	8.2	48.5	3.l	6.0
			Gemcitabine–cisplatin		10.2	70.4	5.3	7.5
					NS	(P<0.001)	HR 0.75 (P=0.053)	HR 0.80 (P=0.15)
Moore et al^Citation13	569	Locally advanced or metastatic	Gemcitabine	OS	8.0	49.2	3.7	5.9
			Gemcitabine–erlotinib		8.6	57.5	3.5	6.2
					NS	(P=0.07)	HR 0.77 (P=0.004)	HR 0.82 (P=0.038)
Poplin et al^Citation14	547	Locally advanced or metastatic	Gemcitabine	OS	6.0	NA	2.6	4.9
			Gemcitabine–oxaliplatin		9.0		2.7	5.7
					NS		(P=0.10)	HR 0.88 (P=0.22)
Cunningham et al^Citation10	533	Locally advanced or metastatic	Gemcitabine	OS	12.4	41.7	3.8	6.2
			Gemcitabine–capecitabine		19.1	48.7	5.3	7.l
					(P=0.034)	NA	HR 0.78 (P=0.004)	HR 0.86 (P=0.08)
Colucci et al^Citation59	400	Locally advanced or metastatic	Gemcitabine	OS	10.1	NA	3.9	8.3
			Gemcitabine–cisplatin		12.9		3.8	7.2
					(P=0.37)		HR 0.97 (P=0.80)	HR 1.10 (P=0.38)
Conroy et al^Citation15	342	Metastatic	Gemcitabine	OS	9.4	50.9	3.3	6.8
			FOLFIRINOX		31.6	70.2	6.4	11.1
					(P<0.001)	(P<0.001)	HR 0.47 (P<0.001)	HR 0.57 (P<0.001)
Von Hoff et al^Citation16	861	Metastatic	Gemcitabine	OS	7.0	33.0	3.7	6.7
			Gemcitabine–nab-paclitaxel		23.0	48.0	5.5	8.5
					(P<0.001)	(P<0.001)	HR 0.69 (P<0.001)	HR 0.72 (P<0.001)

Abbreviations: FOLFIRINOX, 5-fluorouracil, folinic acid, irinotecan and oxaliplatin; HR, hazards ratio; NA, not available; OS, overall survival; PFS, progression-free survival.

Table 2 Ongoing clinical trials investigating the addition of an anti-stroma agent to the combination of gemcitabine and nab-paclitaxel in pancreatic cancer

Trial ID	Agent	Mechanism of action	Patient population	Study design
NCT02005315^106	Vantictumab (OMP18R5)	Human mAb targeting the WNT pathway	1st line, metastatic	Phase 1b dose escalation study
NCT01431794^107	Erismodegib (LDE225)	Oral hedgehog inhibitor	Borderline resectable	Open-label Phase 1/2 randomized study
NCT01088815^108	Vismodegib (GDC-0449)	Oral hedgehog inhibitor	1st line, metastatic	Single arm Phase 2 study
NCT01839487^109	PEGPH20	PEGylated recombinant human hyaluronidase	1st line, metastatic	Open-label Phase 2 randomized study
NCT01804530^110	PLX7486-TsOH	TKI inhibitor tosylate salt	Advanced non-resectable (part 2)	Phase 1 dose-escalation study
NCT01647828^111	OMP-59R5	Anti-notch receptor mAb	1st line, metastatic	Open-label Phase 1/2 randomized study
NCT01461915^112	ODSH	Low anticoagulant heparin derivate	1st line, metastatic	Open-label Phase 2 randomized study
NCT01621243^113	M402	Heparan sulfate mimetic	Metastatic pancreatic cancer	Double-blinded Phase 1/2 randomized study
NCT01844817^114	Apatorsen (OGX-427)	Antisense oligonucleotide targeting HSP 27	1st line, metastatic	Double-blinded Phase 2 randomized study
NCT01858883^115	INCB039110	Selective Janus Kinase-1 inhibitor	Advanced or metastatic	Phase 1b study

Abbreviations: mAb, monoclonal antibody; TKI, tyrosine kinase inhibitor; HSP, heat shock protein; PEGPH20, (PEGylated Recombinant Human Hyaluronidase); ODSH, (2-0, 3-0 Desulfated Heparin).

Table 3 Main clinical trials with gemcitabine and nab-paclitaxel in other treatment settings of pancreatic cancer

Trial ID	Indication	Patient population	Treatment arms	Study design	Primary endpoint
NCT01964430^116	Adjuvant	Resected (R0 or R1) Stage T 1–3, N 0–1, M0	Gemcitabine vs Gemcitabine nab-paclitaxel	Open-label, randomized Phase 3	Disease-free survival
NCT01978184^117	Neoadjuvant	Potentially or borderline respectable	Gemcitabine nab-paclitaxel vs Gemcitabine nab-paclitaxel plus hydroxychloroquine	Open-label Phase 2 randomized study	Histologic response
NCT01470417^118	Neoadjuvant	Resectable and borderline respectable	Low-risk resectable: Gemcitabine nab-paclitaxel followed by surgery High-risk/borderline resectable: Gemcitabine nab-paclitaxel followed by CRT and surgery	Non-randomized Phase 2 study	Biochemical response Radiologic response Pathologic downstaging R0 resection rate
NCT02024009^119	Locally advanced disease	Unresectable, locally advanced	Gemcitabine nab-paclitaxel followed by CRT (50.4 or 60 Gy) with or without Nelfinavir	Randomized Phase 2/3 study	Overall survival

Abbreviation: CRT, chemoradiotherapy.

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