Dosing De Novo Two-Drug Combinations Based On 32,894 Patients In Phase I-Iii Clinical Trials.

2563Background: Metastatic cancers harbor complex genomic alterations. Combinations are needed to attenuate resistance. Knowledge of appropriate starting doses for novel drug combinations in clinical trials and practice is lacking. Literature review was used to help inform selection of safe starting doses for two-drug combinations involving a targeted agent. Methods: Phase I-III adult oncology clinical trial publications (Jan. 1, 2010 to Dec. 31, 2013; PubMed) were reviewed. The dose of drug used in each combination was compared to the single agent recommended dose (FDA-approved/recommended phase 2 dose (RP2D)/maximum tolerated dose (MTD)). Dose percentages were calculated as: (safe dose of drug in combination/dose of drug as single agent at FDA/RP2D/MTD) X 100. Additive dose percentages were the sum of the dose percentage for each drug. Results: 144 studies (N = 8,568 patients; 95 combinations) of dual targeted agents and 372 studies (N = 24,326 patients; 248 drug combinations) with a targeted and cytoto...