Lower Drug Toxicity Experienced in Trials with Biologics
The main reason patients withdraw their participation from clinical trials is drug toxicity. In this study, the investigators aimed to define the risk of serious toxicity in phase 1 clinical trials of molecularly targeted agents (MTA) or biologics. To meet this aim, a retrospective analysis was conducted to define the rate of treatment-related grade 3/4 toxic effects, deaths, and risk factors associated with grade 3 or more toxicity in phase 1 trials of MTAs.
From this meta-analysis of 36 clinical trials (N=687 patients), most participants were capable of self-care and had a high ECOG performance status (PS ≤ 2). “The rate of grade 3 and 4 events was 14.1% (n = 97) and 1.9% (n = 13), respectively; 24% of these events were gastrointestinal, 22% constitutional, and 20% metabolic,” the investigators reported. “A performance status of 2 was associated with a higher risk of toxicity [odds ratio (OR), 2.6; 95% confidence interval (CI) 1.1–6.1; P=0.032] as was receiving >100% of maximum tolerated dose or maximum administered dose (OR 2.5; CI 1.6–3.9; P<0.001).”
Although the investigators concluded that therapy with novel MTAs in phase 1 trials is associated with a moderate risk of significant toxicity, the risk of toxicity appears lower for MTAs than for chemotherapies.