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%.

Bevacizumab-Containing Chemoimmunotherapy for Recurrent Non-Small-Cell Lung Cancer after Chemoradiotherapy: Case Report

“…High rates of PD reaching 28.7% among French patients [7] and 24.2% among Japanese patients [8] have led to early PD in the population. The early PD rate was reported to be similar to that of populations with ultrahigh PD-L1 expression of 90 to 100% [9]. This finding contradicts another report [10].…”

Impact of PD1 and PDL1 immunotherapy on non-small cell lung cancer outcomes: a systematic review

“…Seventeen RCT studies reported progression-free survival (PFS) from up to 3 years patient follow-up 30–41 43 44 93–95. Fifty-two observational studies with short-term follow-up reported PFS 47–58 62–71 73–75 77–84 86–89 91 92 96–103. Heterogeneity in the meta-analysed studies tended to be high; the I 2 statistics for short-term follow-up studies of nivolumab and pembrolizumab were 69% and 91%, respectively.…”

Upregulated immuno-modulator PD-L1 in malignant peripheral nerve sheath tumors provides a potential biomarker and a therapeutic target

“…Thus, PD-L1 expression in the tumor microenvironment will reduce the T cell-based antitumor immune response [10,23,24]. Two anti-PD-1 monoclonal antibodies (nivolumab and pembrolizumab) [25][26][27] and three anti-PD-L1 monoclonal antibodies (atezolizumab, avelumab, and durvalumab) [28][29][30] have been approved by the US Food and Drug Administration (FDA) for treating cancers, for example, melanoma, nonsmall cell lung cancer, and renal cell carcinoma. Last year (after we completed the present study), PD-1 inhibition was reported to have achieved a complete metabolic response for a MPNSTs [31].…”