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. 2020 Jan 13;9(1):1710052. doi: 10.1080/2162402X.2019.1710052

Table 2.

Meta-analysis for the effects of combination therapies versus single agents on outcome in randomized trials (multivariate)a.

  Response rate
 PFS
 OS
  N OR (95% CI) N HR (95% CI) N HR (95% CI)
Overall
P-value		 88 1.61 (1.40–1.84)
<0.001		 71 0.75 (0.69–0.81)
<0.001		 48 0.87 (0.81–0.94)
<0.001
Class of backbone drug
Targeted small molecule inhibitors
Targeted monoclonal antibodies
Immunotherapy
Hormonal
Not classifiedb 		33
12
9
31
3		 1.31 (1.07–1.61)
p = .01
2.17 (1.55–3.02)
p < .001
2.13 (1.38–3.28)
p < .001
1.54 (1.27–1.87)
p < .001
4.71 (1.90–11.67)
p = .001		 29
12
3
25
2		 0.90 (0,59–1.36)p = .60
0.87 (0.53–1.44)
p = .59
0.64 (0.36–1.12)
p = .11
0.69 (0.61–0.78)
p < .001
1.32 (0.82–2.14)
p = .25		 24
8
3
11
2		 0.82 (0.57–1.17)
p = .26
0.57 (0.38–0.85)
p = .007
0.49 (0.33–0.74)
p = .001
0.95 (0.78–1.17)
p = .65
1.61 (0.97–2.65)
p = .06
Tumor Type
Breast Cancer
Colorectal Cancer
NSCLC
Prostate Cancer
RCC
Others 		28
5
21
6
12
16		 NS
NS
NS
NS
NS
NS		 24
4
20
5
10
8		 0.90 (0.59–1.36)
p = .60
0.83 (0.56–1.24)
p = .36
0.83 (0.73–0.94)
0.005
0.50 (0.29–0.86)
p = .01
0.82 (0.64–1.05)
p = .11
0.92 (0.72–1.18)
p = .50		 9
4
18
6
7
4		 0.82 (0.57–1.17)
p = .26
1.55 (0.94–2.56)
p = .08
1.32 (1.01–1.71)
p = .04
0.54 (0.38–0.77)
p = .001
1.27 (1.02–1.59)
0.035
0.98 (0.83–1.14)
p = .75
Median Number Prior Regimensc
0
1
2
3 or more 		35
35
11
5		 NS
NS
NS
NS		 33
27
9
2		 NS
NS
NS
NS		 19
19
8
2		 0.82 (0.57–1.17)
p = .26
0.59 (0.40–0.87)
p = .008
0.70 (0.45–1.07)
p = .09
0.76 (0.58–0.99)
p = .04

aSingle agents are the reference point for all statistics. The final model included the following variables in each category: RR (Backbone drug class and linear start of enrollment year); OS (backbone drug class, tumor indication, and median prior regimens); PFS (backbone drug class and tumor indication).

bNot Classified included: prednisone, lenalidomide, cimetidine, retinoic acid, simvastatin, zoledronic acid, alendronate, sargramostim. For a full list of classification of agents see Supplemental Table 1.

cTwo trials included in response rate analysis did not reported number of prior regimens.

Abbreviations: HR, hazard ratio; mAB: monoclonal antibody; N, number of randomized comparisons included; NS: not significant in (and therefore not included in) multivariate model; NSCLC: non-small cell lung cancer; OS, overall survival; PFS, progression-free survival; OR, odds ratio; RCC: renal cell carcinoma.