The efficacy outcomes in non-small cell lung cancer patients treated with PD axis inhibitor agents - a population-based study of the Vojvodina region.

Background: By 2021, the FDA approved the use of the drugs pembrolizumab and atezolizumab in the first-line treatment of patients with high positivity of programmed death ligand-1 (PD-L1) in locally advanced and metastatic non-small-cell-lung cancer (NSCLC). This approval was the result of statistically significant evidence from international, multicentric clinical studies that all reported increasing progression-free survival (PFS) and overall survival (OS) in these patients. Methods: In our study, we reported the demographic and clinical characteristics of 79 patients diagnosed with NSCLC with expression of PD-L1 ≥50% from January 2019 to December 2022 at the Institute for Pulmonary Diseases of Vojvodina, who received pembrolizumab therapy as the first-line treatment. Patients were divided according to the histological type of lung cancer as adenocarcinoma (ADC) or squamous cell carcinoma (SCC) of the lung. In 52 of the 79 patients, PFS and in 32 of them overall survival (censored OS) was shown according to the histological type of tumor, the tumor proportion score (TPS) of PDL-1 expression, and the metastatic status within the Tumor Nodes Metastasis (TNM) disease classification. Independent factors of death outcome were shown by multivariable proportional hazard regression analysis. Results: The study included 79 patients diagnosed with NSCLC with an expression of PD-L1 ≥50%, 50 (63.3%) patients with ADC, and 29 (36.7%) patients with SCC, whose 55 (69.6%) PDL-1 expression was obtained from broncho biopsy (BB). The majority of patients, 49 (62%), had a TPS PD-L1 score of 51%-79%. Median, PFS for adenocarcinoma was 22 months and censored OS was 27 months, while for squamous cell carcinoma, median PFS was 12 months, and censored OS was 21 months. M1b disease stage, which was the most common in patients, had a PFS of 16 months and a censored OS of 18 months. Conclusion: Pembrolizumab monotherapy in patients with NSCLC in the fourth stage of the disease and with the positivity of the immune checkpoint protein TPS PD-L1 above 50% represents a safe therapy that allows a satisfactory period without disease progression and overall survival with acceptable treatment complications.

Lalić N ，Bojović M ，Bursać D ，Bokan D ，Čeriman Krstić V ，Kuhajda I ，Parapid B ，Tomić S ，Šipka A ... -  《-》

Differential Efficacy of Pembrolizumab According to Metastatic Sites in Patients With PD-L1 Strongly Positive (TPS ≥ 50%) NSCLC.

Pembrolizumab has shown significantly better efficacy than platinum doublet chemotherapy in patients with programmed cell death ligand 1 (PD-L1) strongly positive (tumor proportion score ≥ 50%) non-small-cell lung cancer (NSCLC). However, the predictors of response to pembrolizumab have not yet been fully elucidated for patients with PD-L1 strongly positive NSCLC. We retrospectively analyzed 145 patients who had been treated with pembrolizumab for PD-L1 strongly positive (TPS ≥ 50%) NSCLC without an EGFR (epidermal growth factor receptor) mutation or ALK rearrangement from February 2017 to March 2020. Various clinical characteristics, including Eastern Cooperative Oncology Group performance status, treatment line, PD-L1 expression, C-reactive protein level, neutrophil/lymphocyte ratio, and metastatic sites, and the clinical outcome of pembrolizumab treatment were examined. Patients with higher PD-L1 expression (≥ 75%; n = 90) had a higher objective response rate (ORR) and longer progression-free survival (PFS) compared with those with lower expression (50%-74%; n = 55; ORR, 51% vs. 33%; P = .0305; median PFS, 13.9 months vs. 5.2 months; P = .0111). In addition, 15 patients with liver metastasis (LM) had a significantly lower ORR and shorter PFS than the 130 patients without LM (ORR, 20% vs. 47%; P = .0468; median PFS, 3.4 months vs. 9.4 months; P = .0018). A multivariate analysis indicated that PD-L1 expression and LM were significant predictors of PFS after pembrolizumab treatment (higher PD-L1 expression: hazard ratio, 0.58; 95% confidence interval, 0.38-0.91; P = .0183; presence of LM: hazard ratio, 2.05; 95% confidence interval, 1.03-3.82; P = .0420). PD-L1 expression and LM status were predictors of the efficacy of pembrolizumab in patients with PD-L1 strongly positive NSCLC.

Takeyasu Y ，Yoshida T ，Shibaki R ，Matsumoto Y ，Goto Y ，Kanda S ，Horinouchi H ，Yamamoto N ，Motoi N ，Ohe Y ... -  《-》

Pretreatment Glasgow prognostic score predicts survival among patients with high PD-L1 expression administered first-line pembrolizumab monotherapy for non-small cell lung cancer.

There are no established biomarkers for predicting the efficacy of first-line pembrolizumab monotherapy in patients with high programmed death-ligand 1 (PD-L1) expression. In this study, we investigated whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can be used to evaluate the effect of first-line pembrolizumab monotherapy in patients with advanced non-small cell lung cancer (NSCLC) who express high levels of PD-L1. We reviewed data from 142 patients with high PD-L1 expression who underwent first-line pembrolizumab monotherapy for NSCLC at six Japanese institutions between February 2017 and June 2019 and assessed the prognostic value of the GPS, NLR, and BMI. The Kaplan-Meier method and Cox proportional hazard models were used to examine differences in progression-free survival (PFS) and overall survival (OS). The GPS, NLR, and BMI were calculated using C-reactive protein and albumin concentrations, neutrophil and lymphocyte counts, and body weight and height, respectively. The GPS independently predicted the first-line pembrolizumab monotherapy efficacy, as a good GPS (GPS 0-1) was associated with a significantly better PFS and OS compared to a poor GPS (GPS 2) (PFS: 11.8 vs. 2.9 months, p < 0.0001; OS: not reached vs. 8.3 months, p < 0.0001). Furthermore, BMI independently predicted efficacy, as patients with high BMI (BMI ≥21.4) exhibited significantly better OS compared to those with low BMI (BMI <21.4) (OS: not reached vs. 14.1 months, p = 0.006). Among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC, the GPS is significantly correlated with both PFS and OS, and BMI with OS, indicating that they could be used to predict treatment outcome in these patients. To the best of our knowledge, this is the first study to assess the relationship among the GPS, NLR, and BMI and survival among patients with high PD-L1 expression undergoing first-line pembrolizumab monotherapy for NSCLC.

Imai H ，Kishikawa T ，Minemura H ，Yamada Y ，Ibe T ，Yamaguchi O ，Mouri A ，Hamamoto Y ，Kanazawa K ，Kasai T ，Kaira K ，Kaburagi T ，Minato K ，Kobayashi K ，Kagamu H ... -  《Cancer Medicine》

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 ... -  《-》

Programmed Death-Ligand 1 Tumor Proportion Score and Overall Survival From First-Line Pembrolizumab in Patients With Nonsquamous Versus Squamous NSCLC.

For patients with NSCLC receiving immune checkpoint inhibitors, programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) has been validated as a predictive biomarker for improved overall survival (OS). Nevertheless, its histology-specific predictive value in patients with advanced squamous versus nonsquamous cancers remains unclear. To evaluate the differential value of PD-L1 TPS as a predictive biomarker for OS after first-line pembrolizumab in patients with squamous versus nonsquamous NSCLC. Retrospective, observational study of patients diagnosed with having advanced NSCLC who were treated between October 2015 and April 2019 at community oncology clinics and academic medical centers in a deidentified electronic health record-derived database. Included patients were diagnosed with having advanced or metastatic NSCLC, received treatment with first-line, single-agent pembrolizumab, and had documentation of PD-L1 testing with a numeric result. Exclusion criteria included alterations in EGFR, ALK, and ROS1. The primary end point was OS from start of first-line pembrolizumab therapy by squamous or nonsquamous histology and PD-1 expression level measured by TPS (low, <50% or high, ≥50%). The cohort of 1460 patients with NSCLC who received pembrolizumab as a first-line therapy had a mean age of 72 years. Histology was 28% squamous and 72% nonsquamous. PD-L1 expression was low in 13% and high in 87%. No meaningful differences in age, sex, or smoking history were observed by PD-L1 TPS or histology type. A generalized gamma model adjusting for sex and stage at diagnosis found that for patients with nonsquamous histology, high PD-L1 TPS was significantly associated with improved OS by a median OS difference of 8.4 months (p < 0.001). In contrast, for patients with squamous histology, there was no evidence of association between PD-L1 expression level and OS (p = 0.283). PD-L1-related incremental differences in median OS between the patients with squamous and nonsquamous tumors were significantly different (p = 0.034). Among patients with NSCLC treated with first-line pembrolizumab, high PD-L1 TPS is associated with OS among patients with nonsquamous NSCLC, but not among patients with squamous NSCLC.

Doroshow DB ，Wei W ，Gupta S ，Zugazagoitia J ，Robbins C ，Adamson B ，Rimm DL ... -  《-》