Gouda M A, Ballesteros P A, Garrido-Laguna I, Rodon J
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, USA.
Department of Medical Oncology, Hospital Universitario 12 de Octubre, Madrid, Spain.
Ann Oncol. 2025 May;36(5):507-519. doi: 10.1016/j.annonc.2025.02.010. Epub 2025 Mar 4.
The scope of phase I clinical trials in oncology goes beyond the conventional safety evaluation-only objectives of these trials in other specialties. Rather, most first-in-human oncology clinical trials have therapeutic intent, and efficacy signals observed in phase I trials can drive a go/no-go decision of advancing a new molecule to phase II testing. The complexity of efficacy assessment in the context of a small, heterogeneous patient population and a complex study design requires a more liberal perspective compared with later trial phases when looking into efficacy endpoints. Classically, in later-phase clinical trials, these endpoints would include the objective response rate, progression-free survival, and overall survival. However, new, evolving endpoints may be worth investigating when looking into the antitumor activity signals in phase I trials. Integration of all these endpoints into trial designs can improve the assessment of therapeutic efficacy during early drug development and guide decisions related to the further advancement of novel molecules into later phases. In this review, we discuss the advantages and pitfalls of different classic efficacy endpoints when evaluated as part of phase I trials in oncology and describe how challenges in assessing the antitumor activity of new drugs can be overcome through the incorporation of novel endpoints that have thus far proven successful in clinical trials.
肿瘤学中一期临床试验的范围超出了这些试验在其他专业中仅进行常规安全性评估的目标。相反，大多数首次人体肿瘤学临床试验都有治疗意图，并且在一期试验中观察到的疗效信号可以推动关于将新分子推进到二期试验的继续/终止决策。在小型、异质性患者群体和复杂研究设计的背景下进行疗效评估的复杂性，与后期试验阶段在研究疗效终点时相比，需要一种更宽松的视角。传统上，在后期临床试验中，这些终点将包括客观缓解率、无进展生存期和总生存期。然而，在研究一期试验中的抗肿瘤活性信号时，新出现的、不断演变的终点可能值得研究。将所有这些终点整合到试验设计中，可以改善早期药物开发过程中对治疗效果的评估，并指导与将新分子进一步推进到后期阶段相关的决策。在这篇综述中，我们讨论了在作为肿瘤学一期试验的一部分进行评估时，不同经典疗效终点的优势和缺陷，并描述了如何通过纳入迄今已在临床试验中证明成功的新终点来克服评估新药抗肿瘤活性方面的挑战。
