Nanoparticle albumin-bound (nab)-paclitaxel for the treatment of pancreas ductal adenocarcinoma

Figures & data

Table 1 Factors implicated in high mortality of pancreatic adenocarcinoma

Patient factors	Nonspecific symptoms Advanced age, comorbidity (DM, VTE) Unresectable stage at presentation
Ineffective screening	Paucity of biomarkers to identify patients at risk Expensive and invasive modalities (MRI, EUS)
Tumor microenvironment	Desmoplastic tumor stroma
	Relatively avascular and hypoxic tumor milieu
Treatment	Toxicity of multiagent chemotherapy Complex radiation field, radiation resistance Genetic heterogeneity

Abbreviations: DM, diabetes mellitus; VTE, venous thromboembolism; MRI, magnetic resonance imaging; EUS, endoscopic ultrasound.

Table 2 Differences between solvent-based paclitaxel and nab-paclitaxel

	SB-paclitaxel	Nab-paclitaxel
Solvent	Castor oil-based	Solvent-free
Pharmacokinetics	Nonlinear	Linear
Hypersensitivity	Common	None
Premedication	Steroids, antihistamines	Not required
Special infusion tubing	Required	Not required
Infusion time	3 hours	30 minutes

Abbreviation: SB, solvent-based.

Table 3 Proposed mechanisms for efficacy of nab-paclitaxel in pancreatic cancer in preclinical studies

Barrier	Proposed MOA of nab-paclitaxel	Effect
Impaired drug delivery	Transcytosis by gp60, caveolin Endocytosis by SPARC	Peritumoral drug delivery Intratumoral drug delivery
Desmoplastic stroma	Stromal depletion	Impaired tumor defense
Macropinocytosis of albumin	Engulfment of albumin-bound paclitaxel	Intratumoral drug delivery
Gemcitabine resistance	Cytidine deaminase inhibition	Increased intratumoral gemcitabine

Abbreviations: MOA, mechanism of action; gp60, glycoprotein 60; SPARC, secreted protein, acidic and rich in cysteine.

Table 4 Comparison of results from the MPACT and FOLFIRINOX trials

Study (n)	Median OS months	Median PFS months	ORR	One-year survival
Gemcitabine^* (n=430)	6.7	3.7	7%	22%
Nab-paclitaxel + gemcitabine (n=431)	8.5	5.5	23%	35%
FOLFIRINOX (n=342)	12.2	6.4	31.6%	48.4%

Notes:

* Gemcitabine control cohort from MPACT trial (results comparable with FOLFIRINOX control group).

Abbreviations: FOLFIRINOX, 5-fluorouracil, leucovorin, irinotecan, oxaliplatin; OS, overall survival; PFS, progression-free survival; ORR, overall response rate.

Table 5 Ongoing clinical trials involving nab-paclitaxel in the treatment of non-metastatic PDA, stratified by treatment setting (according to http://www.clinicaltrials.gov, accessed September 2014)

Clinical trial identifier	Setting	Medications studied	Phase	Status	Estimated completion date
NCT01431794	Neoadjuvant; borderline resectable	nab-Pac + Gem + LDE-225	I/II	Recruiting	September 2016
NCT02210559	Neoadjuvant; locally advanced. unresectable	nab-Pac + Gem ± FG-3019	II	Recruiting	July 2016
NCT02125136	Neoadjuvant; locally advanced	nab-Pac + Gem versus FOFIRINOX	II	Not yet recruiting	December 2017
NCT01470417	Neoadjuvant	nab-Pac + Gem versus nab-Pac + Gem + radiotherapy	II	Ongoing. not recruiting	January 2014
NCT01726582	Neoadjuvant	nab-Pac + Gem versus other^*	II	Recruiting	June 2015
NCT01298011	Neoadjuvant	nab-Pac + Gem	II	Ongoing. not recruiting	December 2013
NCT02047513	Neoadjuvant + adjuvant versus adjuvant only; resectable	nab-Pac + Gem	II	Not yet recruiting	March 2019
NCT01978184	Neoadjuvant. potentially resectable	nab-Pac + Gem ± hydroxychloroquine	II	Recruiting	November 2017
NCT02243007	Neoadjuvant	nab-Pac + Gem versus FOLFIRINOX	II	Not yet recruiting	July 2018
NCT01964430	Adjuvant	nab-Pac + Gem versus Gem	III	Recruiting	Apr1l 2019
NCT02023021	Adjuvant	nab-Pac + Gem	II	Recruiting	May 2017
NCT02043730	Locally advanced. unresectable	nab-Pac + Gem versus Gem alone	II	Ongoing. not recruiting	January 2017
NCT01844817	Metastatic	nab-Pac + Gem ± OGX-427	II	Recruiting	May 2016
NCT01839487	Metastatic. previously untreated	nab-Pac + Gem + PEGPH20 versus nab-Pac + Gem	II	Recruiting	Apr1l 2016
NCT01834235	Metastatic. locally advanced. or unresectable	nab-Pac + Gem ± NPC-IC	I. II	Recruiting	October 2015
NCT01461915	Metastatic	nab-Pac + Gem ± ODSH	II	Recruiting	March 2013
NCT02101021	Metastatic, first line	nab-Pac + Gem + momelotinib	II	Recruiting	September 2016

Notes:

* Treatment regimen to be chosen based on molecular profiling. LDE-225 is a Hedgehog inhibitor; FG-3019 is an anti-fibrotic antibody; and NPC-1C is a chimeric monoclonal antibody.

Abbreviations: nab-Pac, nab-paclitaxel; Gem, gemcitabine; FOLFIRINOX, 5-fluorouracil, leucovorin, irinotecan, oxaliplatin; ODSH, 2-0, 3-0 desulfated heparin.