Pancreatic Cancer: A Review of Current Treatment and Novel Therapies

Figures & data

Table 1. Criteria for resectability per the National Comprehensive Cancer Network (NCCN) and MD Anderson Cancer Center (MDACC) [7].

	Resectable		Borderline Resectable			Locally advanced
	NCCN	MDACC		NCCN	MDACC	NCCN	MDACC
SMV/PV	No tumor contact or under <180° contact without irregularity	Patent		Tumor abutment ≥180° +/= vessel irregularity. Amenable to reconstruction	Short segment occlusion with suitable vessel above/below for reconstruction	Tumor involvement or occlusion that is not amenable to reconstruction	Occluded with no technical reconstructive option
SMA/hepatic artery	No contact	No contact, normal fatty plane		Tumor abutment <180° of circumference of vessel wall	Tumor abutment ≤180° of circumference of vessel wall	Tumor encasement ≥180° of circumference of vessel wall	Encased (≥180° vessel involvement)
CHA	No contact	No contact		Reconstructable, short-segment interface between tumor and vessel of any degree	Short segment encasement/abutment	Not reconstructable, or long-segment encasement	Encased and no reconstructive option

SMV: Superior mesenteric vein. PV: portal vein. CHA: Common hepatic artery.

NCCN: National Comprehensive Cancer Network. MDACC: MD Anderson Cancer Center.

Table 2. Recent trials on neoadjuvant chemotherapy, resectability and outcomes.

Study	Design	Local stage	Chemotherapy	n	Resectability	R0 rate	Median OS (months)
McKenzie 2013	Phase 2 trial	Res	Gem/nP	25	80.0%	95%	NA
O’Reilly 2014	Phase 2 trial	Res	Gem/oxaliplatin	38	71.0%	74%	27.2
Sliesoraitis 2014	Phase 2 trial	Res/BR	Gem/nP vs surgery	32 (10 vs 22)	80% vs 100%	60% vs 77%	NA
Ielpo 2016	Phase 2 trial	Res/BR	Gem/nP	25	68.0%	100%	21
Katz 2016	Phase 1/2 trial	BR	mFOLFIRINOX	22	68.0%	93%	21.7
Okada 2017	Phase 1 trial	BR	Gem/nP	10	80.0%	70%	NA
Tsai 2018	Phase 2 trial	Res/BR	5-FU or gemcitabine-based chemotherapy, depending on molecular profiling	130	82.0%	81%	38
Reni 2018	Phase 2/3 trial	BR/LA	Gem/nP vs Gem/nP/cis/cap	54 (28 vs 26)	32% vs 31%		NA
Murphy 2018	Phase 2 trial	BR	FOLFIRINOX + CRT	48	66.6%	97%	37.7
De Marsh 2018	Phase 2 trial	Res	FOLFIRINOX	21	81.0%	94%	34
Wei 2019	Phase 2 trial	Res	Gem/erlotinib	114	73.0%	81%	21.3
Barbour 2020	Phase 2 trial	Res	Gem/nP	42	71.4%	86%	23.5
Sohal 2020	Phase 2 trial	Res	FOLFIRINOX vs Gem/nP	55 vs 47	73% vs 70%	85% vs 85%	22.4 vs 23.6

Abbreviations: Gem = gemcitabine, nP = nab-paclitaxel, CRT = chemoradiation therapy, OS = overall survival, Res: resectable, BR: borderline resectable.

Table 3. List of selected early phase clinical trials involving targeted therapies in PDAC.

Target	Drug	Trial Phase	NCT Number
KRAS	TCR-T (G12V)	I	NCT04146298
	Exosomes (G12D)	I	NCT03608631
	LY3537982 (G12C)*	I	NCT04956640
	Anti-KRAS G12V mTCR PBL	I	NCT03190941
	anti-KRAS G12D mTCR PBL	I	NCT03745326
	MRTX849 **	II	NCT03785249
	ELI-002 ***	I	NCT04853017
CDKN2A	SY 5609 (CDK7)	I	NCT04247126
	Palbociclib (CDK 4/6) ***	I	NCT03065062
BRCA 1 or 2	Olaparib + pembrolizumab
	Vs Olaparib Alone	II	NCT04548752
BRCA1, 2, PALB2	Adjuvant Olaparib
	Vs Placebo (APOLLO Trial)	II	NCT04858334
ATM	ATR inhibitors
PIK3CA	Taselisib (MATCH)	II	NCT02465060
ROS1	Crizotinib (MATCH)	II	NCT02465060
BRAF	Dabrafenib/trametinib	II	NCT02465060
ERBB2	T-DXd	II	NCT04482309
CTNNB1	Tegavivint	II	NCT04851119
NF1	Trametinib (MATCH)	II	NCT02465060
FGFR1	Trametinib (MATCH)	II	NCT02465060
TP53	SGT53+ GEM + NabP	II	NCT02340117

*Being studied in combination with other compounds Abemaciclib, Erlotinb, Pembrolizumab, Temuterkib, LY3295668, Cetuximab, TNO155.

**Being studied in combination with Pembrolizumab, Cetuximab, Afatinib.

*** ELI-002 2 P (Amph modified KRAS peptides, Amph-G12D and Amph-G12R admixed with admixed Amph-CpG-7909) will be evaluated, with plans to transition to the ELI-002 7 P drug product containing all 7 Amph-Peptides (G12D, G12R, G12V, G12A, G12C, G12S, G13D) in future clinical trials.

**** Being studied in combination with PI3K/mTOR Inhibitor Gedatolisib.

MATCH – Molecular Analysis for Therapy Choice clinical Trial.

T-DXd- Trastuzumab Deruxtecan.

GEM- Gemcitabine, NabP- Nanoliposomal Albumin Bound Paclitaxel.

Katz MHG, Marsh R, Herman JM, et al. Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol. 2013;20(8):2787–2795. doi:10.1245/s10434-013-2886-9.

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