Pembrolizumab for Previously Treated, PD-L1-expressing Advanced NSCLC: Real-world Time on Treatment and Overall Survival.

Immune checkpoint inhibitors have been rapidly adopted for therapy of advanced non-small-cell lung cancer (aNSCLC) based on clinical trial findings. Our aim was to examine outcomes in United States oncology practice settings for patients prescribed pembrolizumab monotherapy for previously treated, programmed death ligand-1 (PD-L1)-expressing aNSCLC, thus clinically similar to patients in the KEYNOTE-010 trial. This retrospective observational study used a nationally representative database to identify adult patients with histologically confirmed aNSCLC and PD-L1 tumor proportion score (TPS) ≥ 1% previously treated with platinum-containing chemotherapy (and appropriate tyrosine kinase inhibitor if nonsquamous aNSCLC with EGFR/ALK genomic tumor aberration). Eligible patients initiated pembrolizumab monotherapy from January 1, 2016, to November 29, 2018; data cutoff was May 31, 2019. The Kaplan-Meier method was used to estimate real-world time on treatment (rwToT) and overall survival (OS). The 349 eligible patients included 199 (57%) men; the median age was 68 years (range, 37-84 years); 70 (25%) of 278 patients with known performance status had Eastern Cooperative Oncology Group score ≥ 2. The median patient follow-up was 8.1 months (range, 1 day to 39.2 months). The median rwToT was 4.9 months (95% confidence interval [CI], 3.7-5.8 months) overall and 5.8 months (95% CI, 4.2-6.6 months) for the TPS ≥ 50% cohort (n = 218). The median OS was 13.8 months (95% CI, 11.0-16.5 months) and 16.5 months (95% CI, 13.7-22.0 months) overall and for TPS ≥ 50%, respectively; 12-month survival rates were 54% and 60%, respectively. Patients treated at oncology practices with pembrolizumab monotherapy for previously treated PD-L1-expressing aNSCLC experienced rwToT and OS similar to treatment duration and OS in phase III clinical trial settings.

Velcheti V ，Chandwani S ，Chen X ，Piperdi B ，Burke T ... -  《-》

Outcomes to first-line pembrolizumab in patients with non-small-cell lung cancer and very high PD-L1 expression.

In non-small-cell lung cancers with programmed death-ligand 1 (PD-L1) expression on ≥50% of tumor cells, first-line treatment with the PD-1 inhibitor pembrolizumab improves survival compared with platinum-doublet chemotherapy. Whether higher PD-L1 levels within the expression range of 50%-100% predict for even greater benefit to pembrolizumab is currently unknown. In this multicenter retrospective analysis, we analyzed the impact of PD-L1 expression levels on the overall response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients who received commercial pembrolizumab as first-line treatment of non-small-cell lung cancer (NSCLC) with a PD-L1 expression of ≥50% and negative for genomic alterations in the EGFR and ALK genes . Among 187 patients included in this analysis, the ORR was 44.4% [95% confidence interval (CI) 37.1% to 51.8%], the mPFS was 6.5 months (95% CI 4.5-8.5), and the mOS was not reached. The median PD-L1 expression level among patients who experienced a response to pembrolizumab was significantly higher than among patients with stable or progressive disease (90% versus 75%, P < 0.001). Compared with patients with PD-L1 expression of 50%-89% (N = 107), patients with an expression level of 90%-100% (N = 80) had a significantly higher ORR (60.0% versus 32.7%, P < 0.001), a significantly longer mPFS [14.5 versus 4.1 months, hazard ratio (HR) 0.50 (95% CI 0.33-0.74), P < 0.01], and a significantly longer mOS [not reached versus 15.9 months, HR 0.39 (95% CI 0.21-0.70), P = 0.002]. Among patients with NSCLC and PD-L1 expression of ≥50% treated with first-line pembrolizumab, clinical outcomes are significantly improved in NSCLCs with a PD-L1 expression of ≥90%. These findings have implications for treatment selection as well as for clinical trial interpretation and design.

Aguilar EJ ，Ricciuti B ，Gainor JF ，Kehl KL ，Kravets S ，Dahlberg S ，Nishino M ，Sholl LM ，Adeni A ，Subegdjo S ，Khosrowjerdi S ，Peterson RM ，Digumarthy S ，Liu C ，Sauter J ，Rizvi H ，Arbour KC ，Carter BW ，Heymach JV ，Altan M ，Hellmann MD ，Awad MM ... -  《-》

Real-world outcomes of first-line pembrolizumab plus pemetrexed-carboplatin for metastatic nonsquamous NSCLC at US oncology practices.

Velcheti V ，Hu X ，Piperdi B ，Burke T ... -  《Scientific Reports》

Real-World Outcomes for Advanced Non-Small Cell Lung Cancer Patients Treated With a PD-L1 Inhibitor Beyond Progression.

Clinical trials of anti-programmed cell death ligand 1 (PD-L1) inhibitor to treat advanced non-small-cell lung cancer (aNSCLC) have permitted treatment beyond progression (TBP). However, the outcomes of patients receiving TBP in routine clinical care are unknown. The present retrospective, observational, multicenter analysis evaluated de-identified electronic health record-derived data from community-based clinics in the United States. The patients had confirmed aNSCLC, had started anti-PD-L1 inhibitor therapy (nivolumab, pembrolizumab, or atezolizumab) before October 1, 2018, and had experienced a real-world progression (rwP) event. The study period ended March 31, 2019. The primary objective was to compare the overall survival (OS) of patients who had discontinued immunotherapy ≤ 30 days (non-TBP) compared with > 30 days after rwP (TBP). Descriptive analyses were performed. The Kaplan-Meier method and log-rank test were conducted for OS. An adjusted multivariable Cox proportional hazards regression model was also used. Overall, the data from 4223 patients were analyzed; 2555 (60.5%) and 1668 (39.5%) in the non-TBP and TBP cohorts, respectively. The median treatment duration for the non-TBP and TBP patients was 2.8 and 9.1 months (log-rank test, P < .001), respectively. The TBP group experienced longer unadjusted OS compared with the non-TBP group (11.5 vs. 5.1 months; log-rank test, P < .001). After adjusting for clinically relevant patient characteristics, the TBP OS benefit persisted (adjusted hazard ratio, 0.69; P < .001). TBP with PD-L1 inhibitor therapy is common in aNSCLC routine care and is potentially effective. These results support clinical trial observations likely to affect practice patterns.

Stinchcombe TE ，Miksad RA ，Gossai A ，Griffith SD ，Torres AZ ... -  《-》

Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non-small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study.

Kawachi H ，Tamiya M ，Tamiya A ，Ishii S ，Hirano K ，Matsumoto H ，Fukuda Y ，Yokoyama T ，Kominami R ，Fujimoto D ，Hosoya K ，Suzuki H ，Hirashima T ，Kanazu M ，Sawa N ，Uchida J ，Morita M ，Makio T ，Hara S ，Kumagai T ... -  《-》