Understanding the relationship between the Objective Response Rate (ORR) and survival outcomes, notably Progression-Free Survival (PFS) and Overall Survival (OS), is relevant for assessing the efficacy of regimens in oncology. We evaluate the relationship between ORR, PFS and OS in immuno-oncology (IO) trials. Data from 68 clinical trials submitted to the FDA were evaluated, examining immunotherapy regimens, notably immune checkpoint inhibitors such as anti-programmed death (ligand)-1 [anti-PD-(L)1], cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) inhibitors and combination therapies [e.g., IO + IO, anti-PD-L1 + chemotherapy, anti-PD-L1 + CTLA-4, anti-PD-L1 + TKI (tyrosine kinase inhibitors)]. Studies were included based on their reporting of ORR, PFS, and OS. Of the 68 clinical trials reviewed, 55 were included in the analysis. The correlation between ORR and PFS was moderate across most immunotherapy regimens, indicating that ORR can serve as a useful predictor of short-term disease control. However, the correlation between ORR and OS was weaker, especially in trials including combination therapies, indicating that ORR alone may not reliably predict long-term survival outcomes. ORR predicts PFS better in first-line treatment but declines in later lines and remains a weak OS predictor overall. Differing degrees of correlation between ORR and survival metrics, particularly across treatment lines and combinations, are observed. While ORR can serve as a surrogate marker for PFS in IO trials, its utility in predicting OS is restricted and the interpretation of the relationship between ORR and PFS or OS is a key limitation. Rather, a decline in PFS with increasing ORR may reflect trial differences rather than a direct relationship. Future analyses should adopt better methodologies to capture these dynamics and focus on improving surrogate endpoints for immunotherapy to improve clinical trial design and patient outcomes.
理解客观缓解率（ORR）与生存结局（特别是无进展生存期（PFS）和总生存期（OS））之间的关系对于评估肿瘤学治疗方案的有效性具有重要意义。本研究评估了免疫肿瘤学（IO）试验中ORR、PFS和OS之间的关联。我们分析了提交至美国食品药品监督管理局的68项临床试验数据，重点考察了免疫治疗方案，包括免疫检查点抑制剂（如抗程序性死亡[配体]-1[抗PD-(L)1]药物）、细胞毒性T淋巴细胞相关蛋白-4（CTLA-4）抑制剂以及联合疗法（例如IO+IO、抗PD-L1+化疗、抗PD-L1+CTLA-4、抗PD-L1+TKI[酪氨酸激酶抑制剂]）。研究纳入标准为报告了ORR、PFS和OS数据。在审查的68项临床试验中，共有55项被纳入分析。在大多数免疫治疗方案中，ORR与PFS呈中等程度相关，表明ORR可作为短期疾病控制的有效预测指标。然而，ORR与OS的相关性较弱，尤其是在包含联合疗法的试验中，这表明仅凭ORR可能无法可靠预测长期生存结局。ORR在一线治疗中对PFS的预测能力较强，但在后续治疗线中预测价值下降，且总体上对OS的预测能力较弱。研究观察到ORR与生存指标之间存在不同程度的关联，这种关联性在不同治疗线和联合方案中尤为明显。尽管在IO试验中ORR可作为PFS的替代指标，但其在预测OS方面的应用有限，且对ORR与PFS或OS关系的解读存在关键局限性。实际上，PFS随ORR升高而下降的现象可能反映的是试验差异而非直接关联。未来的分析应采用更优方法捕捉这些动态变化，并致力于改进免疫治疗的替代终点，以优化临床试验设计和改善患者结局。
The Relationship Between Response Rate and Survival Benefits in Randomized Immunotherapy Studies
肿瘤(癌症)患者之家