We thank Tanaka et al¹ and Liang² for their critical comments on our report.³ We extensively discussed the primary end point while planning the protocol. Considering the question, limitations of the center, and examples in prior landmark studies, including IPASS, ENSURE, EURTAC, OPTIMAL,⁴ and the recently reported NEJ009 study,⁵ investigator-assessed progression-free survival (PFS) was felt to be a valid primary end point. Apart from PFS, our other end points, including PFS after second-line treatment and overall survival (OS), were in the same direction, suggesting that the observed benefit in efficacy was in the right direction. Independent central radiologic review requires significant resources, which is a major limitation in investigator-initiated studies. It is unclear whether blinded independent central review (BICR) is always necessary; several studies have found no difference between investigator-assessed PFS and BICR,^6-8 and some have suggested that BICR may actually lead to an exaggeration of PFS.⁹

中文翻译：

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回复T. Tanaka等人和F. Liang。

我们感谢Tanaka等人¹和Liang ²对我们的报告提出的批评意见。³我们在计划协议时广泛讨论了主要终点。考虑到中心的问题，局限性以及以前的里程碑研究的示例，包括IPASS，ENSURE，EURTAC，OPTIMAL ⁴和最近报告的NEJ009研究⁵研究者评估的无进展生存期（PFS）被认为是有效的主要终点。除了PFS，我们的其他终点，包括二线治疗后的PFS和总生存期（OS），都朝着相同的方向发展，这表明所观察到的疗效益处朝着正确的方向发展。独立的中央放射学检查需要大量资源，这在研究者发起的研究中是一个主要限制。目前尚不清楚是否总是需要盲目的独立中央审查（BICR）；几项研究发现，研究者评估的PFS与BICR之间没有区别，^6-8，有些则表明BICR实际上可能导致PFS的夸大。⁹