Adding programmed death 1/programmed death ligand 1 inhibitors to first-line standard-of-care therapy for metastatic colorectal cancer: A meta-analysis

Table 1 Characteristics of included study

Ref.	Study name	Country	Study design	Phase	Regimens	Cases	pMMR/dMMR/unknown	Mean age (range)	Male (%)	Registration ID
Lenz et al[30], 2024	CheckMate 9X8	Canada, Japan, Spain, United States	RCT	Phase II/III	Nivolumab + mFOLFOX6/BEV	127	121/6/0	58.0 (24.0-85.0)	55.0	NCT03414983
					mFOLFOX6/BEV	68	61/7/0	56.0 (24.0-78.0)	72.0
Antoniotti et al[31], 2022	ATEZOTRIBE	Italian	RCT	Phase II	Atezolizumab + FOLFOXIRI/bevacizumab	145	134/8/3	60.0 (52.0-67.0)	57.2	NCT03721653
Antoniotti et al[32], 2024					FOLFOXIRI/bevacizumab	73	68/5/0	61.0 (54.0-66.0)	57.5	-
Wang et al[33], 2024	ASTRUM-015	China	RCT	Phase II/III	Serplulimab + HLX04 + XELOX	57	40/4/13	61.0 (25.0-74.0)	77.2	NCT04547166
					Placebo + bevacizumab + XELOX	57	50/0/7	58.0 (26.0-73.0)	68.4
Redman et al[34], 2022	NA	United States	RCT	Phase II	Avelumab + AdCEA vaccine + FOLFOX6	10	10/0/0	NA	60.0	NCT03050814
					FOLFOX6	10	10/0/0	NA	30.0
Ree et al[35], 2024	METIMMOX	Norway	RCT	Phase II	Nivolumab + FLOX	38	38/0/0	60.5 (43.0-80.0)	47.0	NCT03388190
					FLOX	38	38/0/0	65.0 (38.0-79.0)	61.0
Segal et al[36], 2024	COLUMBIA-1	Australia, Canada, France, Spain, United States	RCT	Phase II	Durvalumab + oleclumab + FOLFOX + bevacizumab	26	26/0/0	63.5 (41.0-80.0)	57.7	NCT04068610
					FOLFOX + bevacizumab	26	26/0/0	56.0 (22.0-72.0)	73.1

RCT: Randomized controlled trials; BEV: Bevacizumab; pMMR: Mismatch repair-proficient; dMMR: DNA mismatch repair; NA: Not available; mFOLFOX6: 5-fluorouracil/leucovorin/oxaliplatin; FOLFOXIRI: Fluorouracil, leucovorin, oxaliplatin, and irinotecan; HLX04: An approved bevacizumab biosimilar; XELOX: Intravenously oxaliplatin [130 mg/m²] and oral capecitabine [1000 mg/m²]; AdCEA: A carcinoembryonic antigen-targeted adenoviral vaccine; FLOX: Oxaliplatin 85 mg/m² day 1 and bolus 5-fluorouracil 500 mg/m² and folinic acid 100 mg days 1-2; FOLFOX: Oxaliplatin 85 mg/m² and folinic acid 400 mg/m² intravenously every 2 weeks on day 1 of every cycle, and 5-fluorouracil 2400 mg/m² intravenously over 46-48 hours every 2 weeks on day 1 and day 2 of every cycle.

Table 2 Quality assessment by Cochrane risk of bias

Ref.	Random sequence generation	Allocation concealment	Blinding	Incomplete outcome data	Selective reporting	Other bias
Lenz et al[30], 2024	L	L	H	L	L	L
Antoniotti et al[31], 2022	L	L	H	L	L	L
Antoniotti et al[32], 2024
Wang et al[33], 2024	L	U	L	L	L	L
Redman et al[34], 2022	L	L	H	L	L	L
Ree et al[35], 2024	L	L	H	L	L	L
Segal et al[36], 2024	L	L	H	L	L	L

L: Lower risk; H: High risk; U: Unclear.