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%.
Abstract Introduction Coronary artery calcium (CAC) score is widely used for risk stratification. However, in patients with established coronary artery disease (CAD), its clinical implication and relationship with plaque vulnerability have not been fully investigated. Purpose We sought to investigate the relationship between CAC score and plaque vulnerability assessed by optical coherence tomography (OCT). Methods Patients with CAD who had both CAC score and OCT prior to percutaneous coronary intervention were included. The patients with a prior history of coronary revascularization were excluded. Patients were divided into five groups based on CAC score; CAC score of 0, 1-99, 100-399, 400-999, and over 1000. Vulnerable features in culprit plaque assessed by OCT were compared among these five groups. Results In 460 patients, the prevalence of lipid-rich plaque, macrophage, and cholesterol crystal significantly differed among the five groups: lowest in the patients with a CAC score of zero. The prevalence of thin-cap fibroatheroma (TCFA) tended to be lower in those with a CAC score of zero (Figure). In the two-group comparison between the group with a CAC score of zero and the other four groups, the prevalence of lipid-rich plaque (60.5 vs. 85.9%, p < 0.001), macrophage (48.8 vs. 74.1%, p < 0.001), TCFA (16.3 vs. 35.0%, p = 0.013), and cholesterol crystal (11.6 vs. 32.9%, p = 0.004) was significantly lower in the patients with CAC score of zero. No significant difference in vulnerable features was observed among the four groups with CAC scores > 0. CAC score of zero was independently negatively associated with the lipid-rich plaque (odds ratio [OR] 0.246, p < 0.001), macrophage (OR 0.348, p = 0.003), TCFA (OR 0.285, p = 0.006), and cholesterol crystal (OR 0.273, p = 0.010) after adjustment with patient characteristics. Conclusion This is the first study that investigated the relationship between CAC score and plaque vulnerability assessed by OCT in patients with known CAD. Patients with CAC score of zero have a significantly lower prevalence of vulnerable plaque features compared to those with CAC score > 0.
Supplementary Data from A Randomized Phase II Study Comparing Nivolumab with Carboplatin–Pemetrexed for <i>EGFR</i>-Mutated NSCLC with Resistance to EGFR Tyrosine Kinase Inhibitors (WJOG8515L)
<p>Percentage changes in sums of diameters of target lesions from baseline over time (<b>A</b>)<sup>a</sup>, and by PD-L1 CPS at nadir in all patients (<b>B</b>), patients with a biopsy (<b>C</b>), and patients with an archival tumor sample (<b>D</b>) <sup>a</sup>Patients could continue to receive study drugs beyond disease progression if they had investigator-assessed clinical benefit and were tolerating study drugs. A includes data from beyond disease progression. CPS, combined positive score; ICI, immune checkpoint inhibitor; N/A, not available; PD-L1, programmed cell death ligand 1.</p>
