Research Article|Articles in Press, 100474

Clinical characteristics and pharmacokinetics change of long-term responders to anti-PD-1 inhibitor among patients with advanced non-small-cell lung cancer

Open AccessPublished:February 10, 2023DOI:
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      Immune checkpoint inhibitors (ICIs) induce long-term, durable responses in patients with advanced non-small-cell lung cancer (NSCLC). However, these responses are limited to a minority of patients, and most responders show disease progression. The purpose of this study was to determine the differences in clinical factors and blood drug concentrations between LTRs (long-term responders) and non-LTRs.

      Materials and Methods

      We retrospectively analyzed consecutive advanced NSCLC patients who received anti-PD-1 inhibitor monotherapy (nivolumab) from December 22, 2015 to May 31, 2017. Patients who obtained a clinical benefit for > 6 months were referred to as “responders”; among these, individuals who demonstrated a durable response for >2 years were defined as “LTRs”. Those with a clinical benefit for < 2 years were defined as “non-LTRs.”


      A total of 212 patients received anti-PD-1 inhibitor monotherapy. The responders accounted for 35% (75/212) of the patients. Of these, 29 (39%) were LTRs, and 46 (61%) were non-LTRs. The overall response rate and median tumor shrinkage in the LTR group were significantly higher than those in the non-LTR group (76% vs. 35%, P<0.0001; and 66% vs. 16%, P<0.001, respectively). The groups showed no significant difference in PD-L1 expression and serum drug concentration at 3- and 6-months post-treatment initiation.


      Significant tumor shrinkage was associated with a long-term response to an anti-PD-1 inhibitor. However, the PD-L1 expression level and pharmacokinetic profile of the inhibitor could not be used to predict the durable response among the responders.



      immune checkpoint inhibitors (ICIs), non-small-cell lung cancer (NSCLC), programmed cell death-1 (PD-1), programmed cell death - ligand 1 (PD-L1), overall survival (OS), pharmacokinetics (PK), performance status (PS), anaplastic lymphoma kinase (ALK), lactate dehydrogenase (LDH), c-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), tumor proportion score (TPS), maximal tumor shrinkage (MTS), progression-free survival (PFS), complete response (CR), partial response (PR), stable disease (SD), long-term responders (LTR), overall response rate (ORR), complete metabolic response (CMR), tumor-infiltrating lymphocyte (TIL), status within the tumor microenvironment (TME)