Introduction: Traditionally, marked tumor shrinkage has been assumed to portend better outcome. We investigated whether depth of tumor response was associated with improved survival outcomes in advanced EGFR‐mutant NCLC. Methods: Individual patient data from randomized trials (EURTAC, IPASS, ENSURE, LUX‐Lung 3, and LUX‐Lung 6) were used. The association of depth of response with progression‐free survival (PFS) and overall survival was examined using landmark analyses. Depth of response based on radiologic assessments at 6 weeks and 12 weeks was calculated as the relative changes in the sum of the longest diameters of the target lesions from baseline. Results: Of 1081 evaluable patients at 6 weeks with no disease progression, 71.2% achieved Response Evaluation Criteria in Solid Tumors response. Using a landmark analysis, EGFR‐TKI was more effective than chemotherapy (PFS hazard ratio = 0.36, p < .0001); and was associated with greater mean tumor shrinkage than chemotherapy (35.1% versus 18.5%, p < .0001). However, there was no significant difference in the relative PFS benefit between treatment groups across the entire spectrum of tumor shrinkage (p = .18 for test of interaction between treatment and continuously measured depth of response). Depth of response at 6 weeks was not associated with PFS when adjusted for treatment effect (hazard ratio = 0.96, p = .78). Similar results were obtained for 12‐week landmark analysis and for OS outcome. Conclusions: The PFS advantage of EGFR‐TKI over chemotherapy in advanced EGFR mutant NCLC is not explained by depth of response at 6 or 12 weeks. It should not be used as a surrogate of benefit in future trials or routine clinical decision making.

中文翻译：

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早期反应深度在预测 EGFR 突变肺癌长期预后中的价值

介绍：传统上，肿瘤明显缩小被认为预示着更好的结果。我们研究了肿瘤反应的深度是否与晚期 EGFR 突变 NCLC 的生存结果改善相关。方法：使用来自随机试验（EURTAC、IPASS、ENSURE、LUX-Lung 3 和 LUX-Lung 6）的个体患者数据。使用标志性分析检查了反应深度与无进展生存期 (PFS) 和总生存期的关联。基于 6 周和 12 周放射学评估的反应深度计算为目标病灶最长直径总和相对于基线的相对变化。结果：在 6 周时没有疾病进展的 1081 名可评估患者中，71.2% 达到了实体瘤反应的反应评估标准。使用地标分析，EGFR-TKI 比化疗更有效（PFS 风险比 = 0.36，p < .0001）；并且与比化疗更大的平均肿瘤缩小相关（35.1% 对 18.5%，p < .0001）。然而，在整个肿瘤缩小范围内，治疗组之间的相对 PFS 获益没有显着差异（p = .18 用于测试治疗和连续测量的反应深度之间的相互作用）。调整治疗效果后，6 周时的反应深度与 PFS 无关（风险比 = 0.96，p = .78）。12 周标志性分析和 OS 结果获得了类似的结果。结论：EGFR-TKI 在晚期 EGFR 突变型 NCLC 中优于化疗的 PFS 优势不能用 6 周或 12 周时的反应深度来解释。