When Less May Be Enough: Dose Selection Strategies for Immune Checkpoint Inhibitors Focusing on AntiPD-(L)1 Agents

AbstractEarly clinical trials investigating antiPD(L)-1 agents rarely reached  a maximum tolerated dose (MTD), and efficacy signals were observed even at the lowest dose levels. Most extended treatment intervals investigated indicated that these drugs do not follow a direct dose-toxicity or dose-efficacy relationship. Within this context and considering the high cost of an tiPD(L)-1 agents, there is a significant debate on whether lower doses or the administration of such agents at an extended interval should be prospectively evaluated in already-approved agents, or at least be considered in novel combination trials involving antiPD(L)-1 drugs. Herein, we review the d osing, overall response rates, and incidence of treatment-related adverse events of antiPD(L)-1 agents in early dose-escalation trials and discuss the appropriateness of recommended Phase 2 dose selection as well as the final regulatory approved doses of such agents. Efficacy and safety data from ra ndomized dose-range Phase 2 trials and real-world data (RWD) on the usage of lower doses and/or non-standard extended treatment intervals are also examined. As the accumulating evidence suggests lower doses or extended dosing intervals of antiPD(L)-1 may achieve a similar clinical benefit in compari son to the currently approved doses, we address the clinical and financial toxicity implications of using potentially higher doses than necessary. Last, we discuss ways to resolve the current dosing conundrum of antiPD...
Source: Targeted Oncology - Category: Cancer & Oncology Source Type: research