Table 3.

Meta-analysis for the effects of combination therapies versus single agents^a upon high-grade toxicities and treatment-related mortality (multivariate^b).

	High-grade toxicity		Treatment-related mortality
	N	OR (95% CI) P value	N	OR (95% CI) P value
Overall P-value	76	2.42 (1.98–2.97) <0.001	87	1.33 (1.15–1.53) <0.001
Class of experimental drug addedc Targeted small molecule inhibitor Targeted monoclonal antibody Immunotherapy Hormonal Not classified	41 19 8 5 3	3.14 (2.49–3.97) p < .001 1.81 (1.24–2.64) p = .002 3.04 (1.76–5.28) p < .001 1.62 (0.85–3.08) p = .14 1.08 (0.43–2.72) p = .86	47 18 10 6 6	1.49 (1.19–1.87) p < .001 1.81 (1.33–2.46) p < .001 1.67 (1.13–2.45) p = .01 2.18 (1.43–3.32) p < .001 0.53 (0.26–1.08) p = .08
Phase of the Study Phase II Phase III	46 30	2.45 (1.82–3.31) p < .0001 2.40 (1.80–3.19) p < .0001	52 35	1.25 (0.93–1.67) p = .13 1.72 (1.31–2.25) p = .003

^aSingle agents are the reference point for all statistics. The final model included the following variables: High-Grade Toxicity (experimental drug class and linear toxicity rate in single arm); Treatment-related mortality (experimental drug class and linear treatment mortality rate in single arm);

^bEstimated ORs in each model are valid after accounting for a linear dependence on the appropriate rate in the single arm. Model chosen using forward selection with entry p-value 0.10

^cClass of experimental drug added to the backbone drug.

Abbreviations: N, number of randomized comparisons included; OR, odds ratio.