Clinical outcomes in non-small cell lung cancer patients with an ultra-high expression of programmed death ligand-1 treated using pembrolizumab as a first-line therapy: A retrospective multicenter cohort study in Japan

Abstract

Background: Pembrolizumab is currently approved as a first-line therapy for advanced non-small cell lung cancer (NSCLC) patients with a programed death ligand-1 (PD-L1) expression ≥50%. However, the association between the efficacy of pembrolizumab and PD-L1 expression levels in patients with PD-L1 expression ≥50% has not been fully elucidated.

Methods: We retrospectively analyzed patients with advanced NSCLC and a PD-L1 tumor proportion score (TPS) of ≥50% who received pembrolizumab as a first-line therapy at 11 institutions in Japan between February 2017 and January 2018. Patients were divided into TPS 50-89% and TPS 90-100% (ultra-high PD-L1 expression) cohorts.

Results: In total, 149 patients were included: 99 (66.4%) and 50 (33.6%) patients were in the TPS 50-89% and TPS 90-100% cohorts, respectively. Baseline characteristics were similar between the TPS 90-100% and TPS 50-89% cohorts. The objective response rates (ORR) in the TPS 90-100% and TPS 50-89% cohorts were 58.0% and 46.5%, respectively (p = 0.23). Time to treatment failure (TTF) was longer in the TPS 90-100% cohort than in the TPS 50-89% cohort (hazard ratio [HR]: 0.67, 95% confidence interval (CI): 0.42-1.07; p = 0.09). Although TTF within 120 days after the initiation of pembrolizumab therapy was comparable between both cohorts (p = 0.54), TTF after 120 days was significantly longer in the TPS 90-100% cohort than in the TPS 50-89% cohort (HR: 0.22, 95% CI: 0.06-0.87; p = 0.031). Immune related adverse events of grade 3 or more occurred in 16.0% and 19.2% of patients in the TPS 90-100% and TPS 50-89% cohorts, respectively.

Conclusions: The patients with an ultra-high PD-L1 expression continued pembrolizumab therapy longer, driven by a reduced risk of treatment failure in the late phase. PD-L1 expression levels might be a predictive biomarker of a first-line immunotherapy benefit in the late phase among NSCLC patients with TPS ≥50%.

Fig 1. Time to treatment failure of pembrolizumab: the tumor proportion score 90–100% cohort versus the tumor proportion score 50–89% cohort.

Panel A shows the Kaplan–Meier survival curves for the time to treatment failure according to the programed death ligand-1 expression levels for the tumor proportion score 90–100% cohort versus the tumor proportion score 50–89% cohort. Panel B shows the Kaplan–Meier survival curves for time to treatment failure before and after 120 days according to the programed death ligand-1 expression levels in landmark analyses. Hazard ratios are for the tumor proportion score 90–100% cohort versus the tumor proportion score 50–89% cohort. The hazard ratios, 95% confidence intervals, and p-values were calculated using univariate Cox regression analysis. Cross marks represent data censored at the last time the patient was known to be alive. Abbreviations: HR, hazard ratio; TPS, tumor proportion score.

Fig 2. Exploratory subgroup analyses of time to treatment failure: The tumor proportion score 90–100% cohort versus the tumor proportion score 50–89% cohort.

Hazard ratios for the time to treatment failure in the tumor proportion score 90–100% cohort versus the tumor proportion score 50–89% cohort. The hazard ratios, 95% confidence intervals, and p-values for each key subgroup were calculated using univariate Cox regression analysis. The response to pembrolizumab was defined as complete and partial responses assessed by the investigator according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Early irAE was defined as irAE that occurred within 3 weeks after commencing pembrolizumab therapy. Abbreviations: HR, hazard ratio; TPS, tumor proportion score; ECOG PS, Eastern Cooperative Oncology Group performance status; irAE, immune-related adverse event.