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

by Ryuya Edahiro, Masaki Kanazu, Hiroyuki Kurebe, Masahide Mori, Daichi Fujimoto, Yoshihiko Taniguchi, Hidekazu Suzuki, Katsuya Hirano, Toshihide Yokoyama, Mitsunori Morita, Yasushi Fukuda, Junji Uchida, Takeshi Makio, Motohiro Tamiya

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%.