Comparison 3. Pembrolizumab versus chemotherapy (post‐hoc included subgroup analyses).

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Overall survival based on age	1		Hazard Ratio (Random, 95% CI)	0.76 [0.60, 0.95]
1.1 < 65 years	1		Hazard Ratio (Random, 95% CI)	0.75 [0.53, 1.06]
1.2 ≥ 65 years	1		Hazard Ratio (Random, 95% CI)	0.76 [0.56, 1.03]
2 Overall survival based on sex	1		Hazard Ratio (Random, 95% CI)	0.74 [0.59, 0.93]
2.1 Male	1		Hazard Ratio (Random, 95% CI)	0.73 [0.56, 0.95]
2.2 Female	1		Hazard Ratio (Random, 95% CI)	0.78 [0.49, 1.24]
3 Overall survival based on smoking status	1		Hazard Ratio (Random, 95% CI)	0.68 [0.41, 1.15]
3.1 Current	1		Hazard Ratio (Random, 95% CI)	0.32 [0.15, 0.68]
3.2 Former	1		Hazard Ratio (Random, 95% CI)	0.71 [0.52, 0.97]
3.3 Never	1		Hazard Ratio (Random, 95% CI)	1.06 [0.72, 1.56]
4 Overall survival based on histologic type	1		Hazard Ratio (Random, 95% CI)	0.72 [0.54, 0.97]
4.1 Transitional cell	1		Hazard Ratio (Random, 95% CI)	0.80 [0.62, 1.03]
4.2 Mixed	1		Hazard Ratio (Random, 95% CI)	0.58 [0.37, 0.91]
5 Overall survival based on PD‐L1 tumour expression status (10% cutoff)	1		Hazard Ratio (Random, 95% CI)	0.71 [0.51, 0.97]
5.1 < 10%	1		Hazard Ratio (Random, 95% CI)	0.80 [0.61, 1.05]
5.2 ≥ 10%	1		Hazard Ratio (Random, 95% CI)	0.57 [0.37, 0.88]
6 Overall survival based on location of primary tumour	1		Hazard Ratio (Random, 95% CI)	0.72 [0.54, 0.95]
6.1 Upper tract	1		Hazard Ratio (Random, 95% CI)	0.53 [0.28, 1.00]
6.2 Lower tract	1		Hazard Ratio (Random, 95% CI)	0.77 [0.60, 0.99]
7 Overall survival based on location of metastases	1		Hazard Ratio (Random, 95% CI)	0.73 [0.59, 0.91]
7.1 Lymph node only	1		Hazard Ratio (Random, 95% CI)	0.46 [0.18, 1.18]
7.2 Visceral disease	1		Hazard Ratio (Random, 95% CI)	0.75 [0.60, 0.94]
8 Overall survival based on liver metastases	1		Hazard Ratio (Random, 95% CI)	0.74 [0.59, 0.94]
8.1 Liver metastases	1		Hazard Ratio (Random, 95% CI)	0.85 [0.61, 1.18]
8.2 No liver metastases	1		Hazard Ratio (Random, 95% CI)	0.67 [0.50, 0.90]
9 Overall survival based on haemoglobin concentration	1		Hazard Ratio (Random, 95% CI)	0.72 [0.57, 0.90]
9.1 < 10 g/dl	1		Hazard Ratio (Random, 95% CI)	0.75 [0.46, 1.22]
9.2 ≥ 10 g/dl	1		Hazard Ratio (Random, 95% CI)	0.71 [0.55, 0.92]
10 Overall survival based on number of risk factors	1		Hazard Ratio (Random, 95% CI)	0.78 [0.62, 0.98]
10.1 No risk factor	1		Hazard Ratio (Random, 95% CI)	0.82 [0.42, 1.60]
10.2 1 risk factor	1		Hazard Ratio (Random, 95% CI)	0.73 [0.49, 1.09]
10.3 2 risk factors	1		Hazard Ratio (Random, 95% CI)	0.84 [0.56, 1.26]
10.4 3 or 4 risk factors	1		Hazard Ratio (Random, 95% CI)	0.76 [0.47, 1.23]
11 Overall survival based on previous platinum therapy	1		Hazard Ratio (Random, 95% CI)	0.73 [0.58, 0.92]
11.1 Cisplatin	1		Hazard Ratio (Random, 95% CI)	0.73 [0.56, 0.95]
11.2 Carboplatin	1		Hazard Ratio (Random, 95% CI)	0.74 [0.47, 1.17]
12 Overall survival based on investigator's choice of chemotherapy	1		Hazard Ratio (Random, 95% CI)	0.73 [0.61, 0.88]
12.1 Paclitaxel	1		Hazard Ratio (Random, 95% CI)	0.76 [0.55, 1.05]
12.2 Docetaxel	1		Hazard Ratio (Random, 95% CI)	0.76 [0.55, 1.05]
12.3 Vinflunine	1		Hazard Ratio (Random, 95% CI)	0.69 [0.51, 0.93]