Predictive Capability of PD-L1 Protein Expression for Patients With Advanced NSCLC: Any Differences Based on Histology?

Noy Meshulami, Sooyun Tavolacci, Diego de Miguel-Perez, Christian Rolfo, Philip C. Mack, Fred R. Hirsch

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations


Lung cancer is responsible for 1.8 million annual deaths. Non–small cell lung cancers (NSCLC) represent 85% of lung cancer tumors. While surgery is an effective early-stage treatment, the majority of newly identified US lung cancer cases are stage III/IV. Immunotherapy, using programmed death-ligand 1 (PD-L1) or programmed death 1 (PD-1) receptor antibody therapeutics, has increased survival for patients with NSCLC. PD-L1 protein expression is widely used as a predictive biomarker informing treatment decisions. However, only a minority of patients (27%-39%) respond to PD-L1/PD-1 treatment. PD-L1 protein expression by immunohistochemistry assay has deficiencies in identifying responding and refractory patients. Given the different characteristics of squamous and nonsquamous NSCLC, the predictability of PD-L1 levels in determining which patients would benefit from immunotherapy could vary between the 2 histologies. We analyzed 17 phase-III clinical studies and a retrospective study to determine if the predictive capability of PD-L1 expression varies between squamous and nonsquamous NSCLC. For patients with NSCLC treated with mono or dual-immune checkpoint inhibitors (ICI), PD-L1 expression was more predictive of benefit for patients with nonsquamous NSCLC than squamous NSCLC. Patients with nonsquamous histology and PD-L1 high tumor proportion scores (TPS) survived 2.0x longer compared to those with low TPS, when treated with monotherapy ICI. Among patients with squamous NSCLC, that difference was 1.2 to 1.3x. For patients treated with ICIs and chemotherapy, there was no clear difference in the predictive value of PD-L1 levels between histologies. We encourage future researchers to analyze the predictability of PD-L1 biomarker expression separately for squamous and nonsquamous NSCLC.

Original languageEnglish
Pages (from-to)401-406
Number of pages6
JournalClinical Lung Cancer
Issue number5
StatePublished - Jul 2023
Externally publishedYes


  • Immune checkpoint inhibitors
  • Immunotherapy
  • Predictive biomarker
  • Squamous vs Nonsquamous
  • Tissue PD-L1 protein expression


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