Neoadjuvant therapy in resectable pancreatic cancer: A promising curative method to improve prognosis

Table 1 Outcomes of randomized controlled trials included in the review

Ref.	Country	NCT number/Name	Treatment arm	N	mOS (mo)	pN0 rate	Resection rate	R0 rate	ITT R0 rate
Golcher et al[7]	Germany	NCT00335543	Upfront surgery	33	14.4	10/33 (30%)	23/33 (70%)	16/23 (70%)	16/33 (48%)
			GEM/CIS + RT	33	17.4	13/33 (39%)	19/33 (58%)	17/19 (89%)	17/33 (52%)
Versteijne et al[8]	Netherlands	PREOPANC	Upfront surgery	68	14.6	NM	54/68 (79%)	32/54 (59%)	32/68 (47%)
			GEM + RT	65	15.6	NM	44/65 (68%)	29/44 (66%)	29/65 (45%)
Casadei et al[9]	Italy	-	Upfront surgery	20	19.5	2/20 (10%)	15/20 (75%)	5/15 (33%)	5/20 (25%)
			GEM + RT	18	22.4	5/18 (28%)	11/18(61%)	7/11 (64%)	7/18 (39%)
Reni et al[10]	Italy	PACT-15	Upfront surgery (GEM)	26	20.4	6/22 (27%)	22/26 (84%)	6/22 (27%)	6/26 (23%)
			Upfront surgery (PEXG)	30	26.4	7/27 (26%)	27/30 (90%)	10/27 (37%)	10/30 (33%)
			PEXG	32	38.2	13/27 (48%)	27/32 (84%)	17/27 (63%)	17/32 (53%)
Satoi et al[11]	Japan	Prep-02/JSAP-05	Upfront surgery	180	26.3	NM	72%	NM	NM
			GEM + S-1	182	36.7	NM	77%	NM	NM

CIS: Cisplatin; GEM: Gemcitabine; RT: Radiotherapy; PEXG: Cisplatin, epirubicin, capecitabine, and gemcitabine; mOS: Median overall survival; pN0: Pathological N0; NM: Not mentioned; ITT: Intention to treat.

Table 2 Ongoing randomized controlled trials comparing surgery alone with neoadjuvant therapy followed by surgery for resectable pancreatic cancer

Trial name	NCT number	Phase	Status	Estimated enrollment	Treatment arm	Primary endpoint	Study start date	Estimated primary completion date	Estimated study completion date
ICI20-00047	NCT05181605	II/III	Not yet recruiting	116	FOLFIRINOX and SBRT with surgery	OS	January 2022	January 2023	December 2024
					Upfront surgery
CISPD-1	NCT03750669	II	Recruiting	416	nPt/GEM and mFOLFIRINOX with surgery	DFS	October 2018	October 2023	October 2024
					Upfront surgery
A021806	NCT04340141	III	Recruiting	352	mFOLFIRINOX with surgery	OS	July 2020	January 2026	November 2030
					Upfront surgery
PREOPANC	NCT04927780	III	Recruiting	378	mFOLFIRINOX with surgery	OS	September 2021	February 2026	July 2029
					Upfront surgery
AIO-PAK-0313	NCT02047513	II	Active, not recruiting	1271	nPt/GEM with surgery	DFS	July 2015	April 20212	October 20223
					Upfront surgery
NorPACT-1	NCT02919787	II/III	Active, not recruiting	140	FOLFIRINOX with surgery	1-yr OS	September 2016	October 2022	April 2026
					Upfront surgery
NEOPAC	NCT01314027	III	Terminated	381	GEM/oxaliplatin with surgery	PFS	September 2009	December 20182	May 20193
					Upfront surgery
NEOPA	NCT01900327	III	Terminated	321	GEM and EBRT with surgery	3-yr survival rate	February 2014	November 20162	July 20173
					Upfront surgery
NEOPAC/IPC 2011-002	NCT01521702	III	Completed	21	GEM/Oxaliplatin with surgery	PFS	December 2011	February 20152	February 20153
					Upfront surgery
NEPAFOX	NCT02172976	II/III	Completed	401	FOLFIRINOX with surgery	mOS	November 2014	January 20202	May 20203
					Upfront surgery

¹Actual enrollment.

²Actual primary completion date.

³Actual study completion date.

SBRT: Stereotactic body radiotherapy; OS: Overall survival; nPt: Nab-paclitaxel; GEM: Gemcitabine; DFS: Disease-free survival; PFS: Progression-free survival; EBRT: External beam radiation.

Table 3 Comparison of median overall survival between the upfront surgery group and the neoadjuvant therapy plus surgery group

Ref.	Country	NCT number/Name	Variable	Upfront surgery	NAT plus surgery	P value
Golcher et al[7]	Germany	NCT00335543	mOS; mo	14.4	17.4	0.96
Versteijne et al[8]	Netherlands	PREOPANC	mOS; mo	14.6	15.6	0.83
Casadei et al[9]	Italy	-	mOS; mo	19.5	22.4	0.97
Reni et al[10]	Italy	PACT-15	mOS; mo	20.4,26.4	38.2	NM
Satoi et al[11]	Japan	Prep-02/JSAP-05	mOS; mo	26.6	36.7	0.015

NAT: Neoadjuvant therapy; mOS: Median overall survival; NM: Not mentioned.

Table 4 Comparison of postoperative complications between the upfront surgery group and the neoadjuvant therapy plus surgery group

Ref.	Country	NCT number/Name	Variable	Upfront surgery	NAT plus surgery	P value
Golcher et al[7]	Germany	NCT00335543	Clavien-Dindo I-II complications	17/33 (52%)	16/33 (48%)	NM
			Clavien-Dindo III-V complications	15/33 (45%)	6/33 (18%)	NM
Versteijne et al[8]	Netherlands	PREOPANC	Postoperative complications	NM	NM	NM
Casadei et al[9]	Italy	-	Post-treatment morbidity	9/20 (45%)	10/18 (56%)	0.746
Reni et al[10]	Italy	PACT-15	Minor complications (Clavien-Dindo I–II)	21/49 (43%)	13/27 (48%)	NM
			Major complications (Clavien-Dindo III–IV)	10/49 (20%)	3/27 (11%)	NM

NAT: Neoadjuvant therapy; NM: Not mentioned.

Table 5 Comparison of tumor size between the upfront surgery group and the neoadjuvant therapy plus surgery group

Ref.	Country	NCT number/Name	Variable	Upfront surgery	NAT plus surgery	P value
Golcher et al[7]	Germany	NCT00335543	Tumoral diameter (cm)	NM	NM	NM
			T1-2 stage	2	4	NM
			T3-4 stage	21	15	NM
Versteijne et al[8]	Netherlands	PREOPANC	Tumoral diameter (cm)	NM	NM	NM
			T1-2 stage	NM	NM	NM
			T3-4 stage	NM	NM	NM
Casadei et al[9]	Italy	-	Tumoral diameter (cm)	NM	NM	NM
			T1-2 stage	0	9	0.016
			T3-4 stage	20	8
Reni et al[10]	Italy	PACT-15	Tumoral diameter (cm)	2.1-2.5	2	NM
			T1-2 stage	3	5	NM
			T3-4 stage	46	22	NM

NAT: Neoadjuvant therapy; NM: Not mentioned.

Table 6 Comparison of resection margin status between the upfront surgery group and the neoadjuvant therapy plus surgery group

Ref.	Country	NCT number/Name	Variable	Upfront surgery	NAT plus surgery	P value
Golcher et al[7]	Germany	NCT00335543	Resection rate	23/33 (70%)	19/33 (58%)	0.31
			R0 rate	16/23 (70%)	17/19 (89%)	NM
			ITT R0 rate	16/33 (48%)	17/33 (52%)	0.81
Versteijne et al[8]	Netherlands	PREOPANC	Resection rate	54/68 (79%)	44/65 (68%)	0.17
			R0 rate	32/54 (59%)	29/44 (66%)	0.54
			ITT R0 rate	32/68 (47%)	29/65 (45%)	NM
Casadei et al[9]	Italy	-	Resection rate	15/20 (75%)	11/18 (61%)	0.489
			R0 rate	5/15 (33%)	7/11 (64%)	NM
			ITT R0 rate	5/20 (25%)	7/18 (39%)	0.489
Reni et al[10]	Italy	PACT-15	Resection rate	49/56 (88%)	27/32 (84%)	NM
			R0 rate	16/49 (33%)	17/27 (63%)	NM
			ITT R0 rate	16/56 (29%)	17/32 (53%)	NM

NAT: Neoadjuvant therapy; NM: Not mentioned; ITT: Intention to treat.

Table 7 Comparison of lymph node status between the upfront surgery group and the neoadjuvant therapy plus surgery group

Ref.	Country	NCT number/Name	Variable	Upfront surgery	NAT plus surgery	P value
Golcher et al[7]	Germany	NCT00335543	pN0	10/33 (30%)	13/33 (39%)	0.44
Versteijne et al[8]	Netherlands	PREOPANC	pN0	NM	NM	NM
Casadei et al[9]	Italy	-	pN0	2/20 (10%)	5/18 (28%)	0.095
Reni et al[10]	Italy	PACT-15	pN0	13/49 (27%)	13/27 (48%)	NM

NAT: Neoadjuvant therapy; pN0: Pathological N0; NM: Not mentioned.