Table 1.

List of studies included in the quantitative analysis and Network Meta-Analysis. NS: not statistically significant according to preplanned statistical analysis

Author/year/ study name	Phase study/ Country	N° randomized patients	Study arms	Hematological toxicity G3-4 (exp arm) N/NF/PLT/Hb	Nonhematological toxicity G3-4 (exp arm) N/V/mucositis/diarrhoea/neurotoxicty	mPFS in months A/B	mOS in months A/B	Primary endpoint	Bias
Oettle/ 2014/ CONKO-003	III/Germany	168	Folinic acid + fluorouracil (FF) (arm A) vs. FF + oxaliplatin (OFF) arm B	NR/NR/1/3	3*/NR/0/3	2.0/2.9  h = 0.68 (SS)	3.3/5.9  h = 0.66 (SS)	OS	LOW
Wang-Gillam/ 2019/ NAPOLI-1	III/Global	417	5-FU/LV (arm A) vs. NALIRI + 5-FU/LV (arm B) vs. NALIRI (arm C)	15.4/NR/5.1/NR	NR/6/NR/9.4/NR	1.5/3.1  h = 0.57 (SS)	4.2/6.2  h = 0.75 (SS)	OS	LOW
Ohkawa/ 2015	IIR/Asia	271	S-1 (arm A) vs. SOX (S-1 + oxaliplatin) (arm B)	8/NR/10/8	6.6/2.9/1.5/5.1/2.9	2.8/3.0  h = 0.84 (NS)	6.9/7.4  h = 1.03 (NS)	PFS	SOME CONCERN
Ioka/ 2017	IIR/Asia	137	S-1 (arm A) vs. IRIS (S-1 + irinotecan) (arm B)	4.6/NR/4.7/15.6	6.3/3/1.6/3.1/NR	1.9/3.5  h = 0.77 (NS)	5.8/6.8  h = 0.75 (NS)	OS	SOME CONCERN
Hurwitz/ 2015/ RECAP	IIR/Western	127	Capecitabine (arm A) vs. capecitabine + Ruxolitinib (arm B)	0/NR/1.7/15.3	5/5/6.8/5/1.7	NA HR = 0.75 (NS)	4.3/4.5  h = 0.79 (NS)	OS	SOME CONCERN
Hecht/ 2021/ SEQUOIA	III/Global	567	FOLFOX (arm A) vs. FOLFOX + Pegilodecakin (arm B)	29.5*/NR/25/16	4/4/NR/4/2	2.1/2.1  h = 0.98 (NS)	5.8/6.3  h = 1.04 (NS)	OS	LOW
Gill/ 2016/ PANCREOX	III/Canada	108	mFOLFOX6 (arm A) vs. 5FU/LV (arm B)	32.7*/4.1/8.2/2	NR/4/NR/2/4	3.1/2.9  h = 0.90 (NS)	6.1/9.9  h = 1.68	OS	LOW
Chiorean/ 2021/ SWOG S1513	IIR/USA	123	FOLFIRI (arm A) vs. FOLFIRI + Veliparib (arm B)	34*/NR/NR/7	12/9/NR/11/NR	2.9/2.1  h = 1.39	6.5/5.4  h = 1.23 (NS)	OS	SOME CONCERN
Ioka/ 2018/ GRAPE	III/Asia	603	TAS-118 (S-1 + LV) (arm A) vs. S-1 (arm B)	1.7/NR/1.7/6	1.7/2/6.7/7.3/NR	3.9/2.8  h = 0.80	7.6/7.9  h = 0.98 (NS)	OS	LOW