Chemo-ICI compared with Chemotherapy in 1st line ES-SCLC
Patient or population: 1st line ES-SCLC Intervention: Chemo-ICI Comparison: Chemotherapy
Outcomes	№ of Participants (Studies) Follow Up	Certainty of the Evidence (GRADE)	Relative Effect (95% CI)	Anticipated Absolute Effects
				Risk with Chemotherapy	Risk Difference with Chemo-ICI
Progression-Free Survival	3952 (10 RCTs)	⨁⨁⨁⨁ HIGH	HR 0.75 (0.70 to 0.80) [Survival]	6 month
				238 per 1000	103 more per 1000 (79 more to 128 more)
Overall Survival	3952 (10 RCTs)	⨁⨁⨁⨁ HIGH	HR 0.78 (0.73 to 0.84) [Survival]	12 month
				400 per 1000	89 more per 1000 (63 more to 112 more)
Objective Response Rate	3952 (10 RCTs)	⨁⨁⨁◯ MODERATE a	RR 1.04 (0.98 to 1.10)	601 per 1000	24 more per 1000 (12 fewer to 60 more)
Duration of Response	2884 (6 RCTs)	⨁⨁⨁◯ MODERATE a	-	The median duration of Response was 3.7 months	MD 0.09 months higher (0.13 lower to 0.32 higher)
Grade 1–4 AE	2719 (7 RCTs)	⨁⨁⨁◯ MODERATE b	RR 1.03 (1.01 to 1.06)	881 per 1000	26 more per 1000 (9 more to 53 more)
Grade 1–4 AE: PD-1/PD-L1	1637 (4 RCTs)	⨁⨁⨁⨁ HIGH	RR 1.02 (1.00 to 1.03)	965 per 1000	19 more per 1000 (0 fewer to 29 more)
Grade 1–4 AE: CTLA-4	1082 (3 RCTs)	⨁⨁⨁⨁ HIGH	RR 1.07 (1.00 to 1.13)	771 per 1000	54 more per 1000 (0 fewer to 100 more)
Grade 3–4 AE	2719 (9 RCTs)	⨁⨁⨁◯ MODERATE a	RR 1.06 (1.00 to 1.12)	557 per 1000	33 more per 1000 (0 fewer to 72 more)
Grade 5 AE	2736 (6 RCTs)	⨁⨁◯◯ LOW c	RR 1.71 (0.90 to 3.25)	12 per 1000	9 more per 1000 (1 fewer to 27 more)
Grade 1–4 Anemia	1499 (5 RCTs)	⨁⨁⨁◯ MODERATE a	RR 0.98 (0.88 to 1.09)	458 per 1000	9 fewer per 1000 (55 fewer to 41 more)
Grade 3–4 Anemia	1644 (6 RCTs)	⨁⨁◯◯ LOW c	RR 0.88 (0.69 to 1.12)	149 per 1000	18 fewer per 1000 (46 fewer to 18 more)
Grade 1–4 Thrombocytopenia	1499 (5 RCTs)	⨁⨁◯◯ LOW c	RR 1.01 (0.85 to 1.21)	218 per 1000	2 more per 1000 (33 fewer to 46 more)
Grade 3–4 Thrombocytopenia	1688 (6 RCTs)	⨁⨁◯◯ LOW c	RR 1.05 (0.79 to 1.41)	93 per 1000	5 more per 1000 (19 fewer to 38 more)
Grade 1–4 Neutropenia	1499 (5 RCTs)	⨁⨁⨁◯ MODERATE a	RR 1.01 (0.90 to 1.13)	451 per 1000	5 more per 1000 (45 fewer to 59 more)
Grade 3–4 Neutropenia	1688 (6 RCTs)	⨁⨁⨁◯ MODERATE a	RR 0.93 (0.81 to 1.07)	313 per 1000	22 fewer per 1000 (60 fewer to 22 more)
Grade 3–4 Febrile Neutropenia	1070 (3 RCTs)	⨁⨁◯◯ LOW c	RR 0.74 (0.44 to 1.24)	60 per 1000	16 fewer per 1000 (34 fewer to 14 more)
Grade 1–4 Fatigue	1499 (5 RCTs)	⨁⨁◯◯ LOW c	RR 1.06 (0.88 to 1.28)	213 per 1000	13 more per 1000 (26 fewer to 60 more)
Grade 3–4 Fatigue	1644 (6 RCTs)	⨁⨁◯◯ LOW c	RR 1.68 (0.91 to 3.10)	19 per 1000	13 more per 1000 (2 fewer to 39 more)
Grade 1–4 Nausea	1521 (5 RCTs)	⨁⨁⨁◯ MODERATE a	RR 1.01 (0.88 to 1.16)	337 per 1000	3 more per 1000 (40 fewer to 54 more)
Grade 3–4 Nausea	1543 (5 RCTs)	⨁⨁◯◯ LOW c	RR 0.42 (0.15 to 1.19)	14 per 1000	8 fewer per 1000 (12 fewer to 3 more)
Grade 1–4 Vomiting	1371 (3 RCTs)	⨁⨁◯◯ LOW c	RR 0.96 (0.75 to 1.23)	155 per 1000	6 fewer per 1000 (39 fewer to 36 more)
Grade 3–4 Vomiting	1374 (3 RCTs)	⨁⨁◯◯ LOW c	RR 0.42 (0.14 to 1.28)	15 per 1000	8 fewer per 1000 (13 fewer to 4 more)
HRQoL	(2 RCTs)	-
The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; HR: Hazard Ratio; RR: Risk ratio; MD: Mean difference
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect