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Comment & Response
August 19, 2021

Immunochemotherapy as First-line Treatment for Locally Advanced or Metastatic Squamous Non–Small Cell Lung Cancers—Reply

Author Affiliations
  • 1State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
  • 2BeiGene (Beijing) Co, Ltd, Beijing, China
  • 3Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China
JAMA Oncol. 2021;7(10):1580-1581. doi:10.1001/jamaoncol.2021.3375

In Reply We would like to thank Huang et al for their comments regarding our recently published phase 3 randomized clinical trial assessing tislelizumab plus chemotherapy vs chemotherapy alone as first-line treatment for advanced squamous non–small cell lung cancer (NSCLC).1 With regard to the points raised, although a numerical difference in progression-free survival (PFS) was seen when patients with programmed cell death 1 ligand 1 (PD-L1) 1% or greater and PD-L1 less than 1% were compared, interaction analyses did not identify a predictive effect of PD-L1 expression for PFS/objective response rate benefit.1 We were unable to make a concrete conclusion, as our study was not designed to detect the difference between high- and low-expression populations. We agree that these results do not align with those from IMpower131,2 where PFS benefit was observed only in PD-L1–positive subgroups, with greater PFS benefit shown in patients with the highest tumor PD-L1 expression. As mentioned, cross-study comparisons should be approached with caution because many factors, including the assays and methods used to score PD-L1 expression, could drive the differences. As there is no universally accepted definition or standard assay for PD-L1 positivity, integration of PD-L1 expression levels into the treatment of NSCLC is challenging. With a growing body of evidence that suggests PD-L1 expression may play more of a predictive role in patients with nonsquamous vs squamous NSCLC,3 there is a significant need to standardize PD-L1 immunohistochemical detection and integrate it with other emerging biomarker evaluations (eg, gene expression profiling, tumor mutation burden).

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