Real-world evidence on first- and second-line palliative chemotherapy in advanced pancreatic cancer

Table 1 Real-world studies of gemcitabine/nab-paclitaxel in the first-line setting[19-23]

Ref.	Location	Study design	Stage M1	n	Regimen	mOS in mo	Subgroup analysis	mPFS in mo	Remarks
Prager et al[19], 2021	Austria	Prospective cohort	100%	317	GnP	10.6/10.2	Age < 70/> 70	5.6/5.5	No difference in frequent toxicities
Blomstrand et al[20,21], 2019/2020	Sweden	Retrospective cohort	71%	75	GnP	10.9	Alb <3 7, age < 65 with shorter survival	5.2	Less hematotoxicity than MPACT
Ostwal et al[22], 2018	India	Retrospective cohort	83%	78	GnP	11.6		5.6	Grade III-IV toxicity 35%
Quinton et al[23], 2018	United Kingdom	Retrospective cohort	100%	74		8.4		-	Hematotoxicity similar to MPACT

GnP: Gemcitabine/Nab-paclitaxel; M1: Metastatic disease; mOS: Median overall survival; mPFS: Median progression-free survival.

Table 2 Real-world studies of Folfirinox in the first-line setting[24]

Ref.	Location	Study design	n	M1	Regimen	mOS in mo	mPFS in mo	Remarks
Cavanna et al[24], 2019	Italy	Retrospective cohort	50	74%	FFX/mFFX	10.1	5.6	mFFX sign less toxicity

FFX: Folfirinox; M1: metastatic disease; mFFX: Modified Folfirinox; mOS: Median overall survival; mPFS: Median progression-free survival.

Table 3 Real-world studies comparing Folfirinox and Gemcitabine/Nab-paclitaxel in the first-line setting[25-32]

Ref.	Location	Study design	n	M1	Regimen	mOS in mo, P value	Prognostic factors	mPFS in mo, P value	Remarks
Franco et al[25], 2020	Spain	Retrospective cohort	119	50%	FFX 59; GnP 60	FFX 12.7; GnP 10.2; P = 0.912	Ca19-9, NLR	-	Toxicity data not reported
Wang et al[26], 2019	Canada	Retrospective cohort	225	58%	FFX 92; GnP 87; Gem 46	FFX 14.1; GnP 10.5; Gem 4.2	-	FFX 8.4; GnP 8.5; Gem 3.7	Sign more hematotoxicity in FFX
Pusceddu et al[27], 2019	-	Review	3813	NA	FFX 1690; GnP 2123	1.15 longer for FFX. P = 0.03	-	-	GnP more neurotoxicity and anemia. FFX more neutropenia
Chiorean et al[28], 2019	-	Review	> 6915	NA	FFX > 3556; GnP > 3359	FFX 15.9; GnP 14.4	-	FFX 11.7; GnP 8.5	FFX more neutropenia, GnP more neuropathy
Papneja et al[29], 2019	Canada	Retrospective cohort	119	77%	FFX 86; GnP 33	FFX 9.0; GnP 9.0	S-Alb, male sex, 2nd line therapy	FFX 6.0; GnP 4.0	Grade 1-2 thromboembolism, mucositis and neuropathy sign more in FFX. Among grade 3-4 toxicity only fatigue sign more in GnP group
Kordes et al[32], 2019	Sweden	Retrospective cohort	595	-	FFX 31; GnP 66; Gem 185	FFX 9.9; GnP 9.8; Gem 6.6	-	-	No sign differences in toxicity comparing FFX vs GnP
Cartwright et al[30], 2018	United States	Retrospective cohort	486	100%	FFX 159; GnP 255; Gem 72	FFX 11.4; GnP 9.8; Gem 4.4	-	-	No sign differences in toxicity comparing FFX vs GnP
Kim et al[31], 2018	United States	Retrospective cohort	654	100%	FFX 317; GnP 337	FFX 13.8; GnP 12.1; P = 0.96	Age	-	Less toxicity in GnP group

FFX: Folfirinox; Gem: Gemcitabine; GnP: Gemcitabine/Nab-paclitaxel; M1: Metastatic disease; mOS: Median overall survival; mPFS: Median progression-free survival; NA: Not applicable; NLR: Neutrophil-leucocyte ratio; s-Alb: Serum albumin.

Table 4 Real-world studies of second-line therapy following failure of Folfirinox[36-44]

Ref.	n	M1	2L regimen	mPFS in mo	mOS in mo	Remarks	AE
Portal et al[36], 2015	57	100%	GnP	5.1	8.8	Prospective cohort	38% grade 3-4 toxicity
Mita et al[37], 2019	30	80%	GnP	3.8	7.6	Phase II	70% grade 3-4 toxicity
Tsang et al[38], 2019	159	67%	GnP 78; Gem 81	-	5.8; 4.6	Population-based, three Canadian provinces	-
Zhang et al[39], 2018	60	73%; 75%; 73%	GnP 30; Gem 8; BSC 22	3.6; 2.5	5.7; 3.8	Single center	More grade 3-4 fatigue in Gem
Nguyen et al[40], 2017	30	77%	GnP	3.7	12.4	Single center	Grade 3-4 thrombocytopenia (33%), anemia (23%), nausea (17%)
Bertocchi et al[41], 2015	23	100%	GnP	3.0	5.0	Single center	-
Zhang et al[42], 2015	28	82%	GnP	3.0	5.7	Single center	Grade 3-4, anemia (25%), thrombocytopenia (25%), neutropenia (18%)
Caparello et al[44], 2016	71	-	GnP	2.5	6.2	Single center	-
Rissy et al[43], 2017	12	100%	GnP	4.9	-	Single-center	No grade 3-4 toxicity reported

BSC: Best supportive care; Gem: Gemcitabine; GnP: Gemcitabine/Nab-paclitaxel; M1: metastatic disease; mOS: Median overall survival; mPFS: Median progression-free survival.

Table 5 Real-world studies of second-line treatment with Folfirinox following failure of gemcitabine/nab-paclitaxel or single-agent gemcitabine[46-51]

Ref.	n	M1	1L regimen	2L regimen	mPFS in mo	mOS in mo	Remarks
Sawada et al[46], 2020	104	100%	GnP	Modified; FFX	3.9	7.0	Bolus 5-FU omitted. 55% grade 3-4 toxicity
Matsumoto et al[47], 2020	23	83%	GnP	FFX 12; mFFX 11	5.3; 4.3	6.9; 12.8	No sign difference in toxicity between FFX/mFFX
Assaf et al[50], 2011	27	100%	Gem	FFX	3.0	8.5	56% grade 3-4 neutropenia
Kobayashi et al[48], 2017	18	100%	Gem	FFX	2.8	9.8	Phase I/II. 83% grade 3-4 toxicity
Kim et al[51], 2018	39	82%	Gem	Attenuated; FFX	3.8	8.5	Oxaliplatin: 65 mg/m2. 41% grade 3-4 neutropenia
Chung et al[49], 2018	48	79%	Gem	Reduced irinotecan and oxaliplatin; FFX	5.8	9.0	Phase IIIrinotecan: 120 mg/m2; Oxaliplatin: 60 mg/m2; 65% grade 3-4 neutropenia

5-FU: Fluorouracil infusion; FFX: Folfirinox; Gem: Gemcitabine; GnP: Gemcitabine/Nab-paclitaxel; M1: Metastatic disease; mFFX: Modified Folfirinox; mOS: Median overall survival; mPFS: Median progression-free survival.