Clinical Characteristics and Pharmacokinetics Change of Long-Term Responders to Antiprogrammed Cell Death Protein 1
Hitomi Jo1,2,3, Tatsuya Yoshida1,4, Shigehiro Yagishita2
1Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Introduction:
Immune checkpoint inhibitors (ICIs) induce long-term, durable responses in patients with advanced NSCLC. Nevertheless, these responses are limited to a few patients, and most responders have disease progression. The purpose of this study was to determine the differences in clinical factors and blood drug concentrations between long-term responders (LTRs) and non-LTRs.
Methods:
We retrospectively analyzed consecutive patients with advanced NSCLC who received antiprogrammed cell death protein 1 (PD-1) inhibitor monotherapy (nivolumab) from December 22, 2015, to May 31, 2017. Patients who obtained a clinical benefit for more than 6 months were referred to as "responders"; among these, individuals who had a durable response for more than 2 years were defined as "LTRs." Those with a clinical benefit for less than 2 years were defined as "non-LTRs."
Results:
A total of 212 patients received anti-PD-1 inhibitor monotherapy. The responders accounted for 35% (75 of 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% versus 35%, p < 0.0001, and 66% versus 16%, p < 0.001, respectively). The groups had no significant difference in PD-L1 expression and serum drug concentration at 3- and 6-month post-treatment initiation.
Conclusions:
Significant tumor shrinkage was associated with a long-term response to an anti-PD-1 inhibitor. Nevertheless, the PD-L1 expression level and pharmacokinetic profile of the inhibitor could not be used to predict the durable response among the responders.
Insights
Significant tumor shrinkage predicts long-term response to immune checkpoint inhibitors (ICIs) in advanced non-small cell lung cancer (NSCLC). However, PD-L1 expression and drug levels do not predict durable responses in NSCLC patients receiving ICIs.
Area of Science:
- Oncology
- Immunotherapy
- Pharmacology
Background:
- Immune checkpoint inhibitors (ICIs) offer durable responses in advanced non-small cell lung cancer (NSCLC), but only for a subset of patients.
- Most patients with advanced NSCLC treated with ICIs experience disease progression, highlighting the need to identify predictors of long-term response.
Purpose of the Study:
- To investigate the clinical factors and blood drug concentrations differentiating long-term responders (LTRs) from non-LTRs in advanced NSCLC patients treated with anti-programmed cell death protein 1 (PD-1) monotherapy.
Main Methods:
- Retrospective analysis of advanced NSCLC patients receiving nivolumab monotherapy.
- Defined LTRs as responders with durable clinical benefit (>2 years) and non-LTRs as those with benefit (<2 years).
- Compared clinical factors, PD-L1 expression, and serum drug concentrations between LTRs and non-LTRs.
Main Results:
- Of 212 patients, 35% responded to anti-PD-1 therapy (75 patients), with 39% (29 patients) classified as LTRs.
- LTRs demonstrated significantly higher overall response rates (76% vs. 35%) and median tumor shrinkage (66% vs. 16%) compared to non-LTRs (p < 0.0001 and p < 0.001, respectively).
- No significant differences were observed in PD-L1 expression or serum drug concentrations at 3 and 6 months between LTRs and non-LTRs.
Conclusions:
- Significant tumor shrinkage is associated with long-term response to anti-PD-1 inhibitors in advanced NSCLC.
- PD-L1 expression levels and drug pharmacokinetic profiles were not predictive of durable responses in this cohort of NSCLC patients.
More Related Videos
04:04Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
06:07Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
