Real-World Prevalence of PD-L1 Expression Among Tumor Samples From Patients With Non–Small-Cell Lung Cancer

Gelatti, A.; Lima, Vladmir Cláudio Cordeiro de; Freitas, Helano; Werutsky, Gustavo; Gaiger, Ana Maria; Klock, Clóvis; Viola, P.; Shiang, Christina; Macêdo, Mariana Petaccia de; Lopes, Lisandro F.; Marchi, Pedro De; Silva, Eduardo Caetano Albino da; Moura, Fernando; Borges, Giuliano Santos; Zaffaroni, Facundo; Filho, Paulo Ricardo Nunes; Araujo, Luiz H.; Mascarenhas, Eldsamira; Mathias, Clarissa; Barrios, Carlos H.; Zukin, Mauro

doi:10.1016/j.cllc.2020.04.007

Cited by 11 publications

(11 citation statements)

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“…PD‐L1 <1% expression was reported in 55.6% of patients enrolled on ADIPemCis, a prevalence that is significantly higher than that reported across key studies of pembrolizumab in NSCLC (33%), but consistent with real‐world data (48%–56.4%) 27–29 . Recent work suggests that arginine deprivation may potentiate immune checkpoint inhibition and turn “cold” tumors “hot” by increasing the PD‐L1 expression and T‐cell infiltration 30,31 .…”

Section: Discussionsupporting

confidence: 61%

Phase 1, pharmacogenomic, dose‐expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1‐deficient non‐squamous non‐small cell lung cancer

et al. 2021

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Introduction We evaluated the arginine‐depleting enzyme pegargiminase (ADI‐PEG20; ADI) with pemetrexed (Pem) and cisplatin (Cis) (ADIPemCis) in ASS1‐deficient non‐squamous non‐small cell lung cancer (NSCLC) via a phase 1 dose‐expansion trial with exploratory biomarker analysis. Methods Sixty‐seven chemonaïve patients with advanced non‐squamous NSCLC were screened, enrolling 21 ASS1‐deficient subjects from March 2015 to July 2017 onto weekly pegargiminase (36 mg/m2) with Pem (500 mg/m2) and Cis (75 mg/m2), every 3 weeks (four cycles maximum), with maintenance Pem or pegargiminase. Safety, pharmacodynamics, immunogenicity, and efficacy were determined; molecular biomarkers were annotated by next‐generation sequencing and PD‐L1 immunohistochemistry. Results ADIPemCis was well‐tolerated. Plasma arginine and citrulline were differentially modulated; pegargiminase antibodies plateaued by week 10. The disease control rate was 85.7% (n = 18/21; 95% CI 63.7%–97%), with a partial response rate of 47.6% (n = 10/21; 95% CI 25.7%–70.2%). The median progression‐free and overall survivals were 4.2 (95% CI 2.9–4.8) and 7.2 (95% CI 5.1–18.4) months, respectively. Two PD‐L1‐expressing (≥1%) patients are alive following subsequent pembrolizumab immunotherapy (9.5%). Tumoral ASS1 deficiency enriched for p53 (64.7%) mutations, and numerically worse median overall survival as compared to ASS1‐proficient disease (10.2 months; n = 29). There was no apparent increase in KRAS mutations (35.3%) and PD‐L1 (<1%) expression (55.6%). Re‐expression of tumoral ASS1 was detected in one patient at progression (n = 1/3). Conclusions ADIPemCis was safe and highly active in patients with ASS1‐deficient non‐squamous NSCLC, however, survival was poor overall. ASS1 loss was co‐associated with p53 mutations. Therapies incorporating pegargiminase merit further evaluation in ASS1‐deficient and treatment‐refractory NSCLC.

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Section: Discussionsupporting

confidence: 61%

Phase 1, pharmacogenomic, dose‐expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1‐deficient non‐squamous non‐small cell lung cancer

et al. 2021

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“…In addition, cytological specimens were not included in the analysis. Recently, Gelatti et al reported lower prevalence in Brazilian cohort with 43.46% of NSCLC patients with score ≥ 1% of PD-L1 expression and 17.83 ≥ 50% [ 20 ]. In all four studies, PD-L1 expression was evaluated by staining with Dako PD-L1 IHC 22C3 pharmDx kit.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy

2020

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Background Expression of PD-L1 is the most investigated predictor of benefit from immune checkpoint blockade in advanced NSCLC but little is known about the association of PD-L1 expression and clinicopathological parameters of patients with unresectable stage III NSCLC. Methods National registry data was searched for medical records of consecutive inoperable stage III NSCLC patients treated with ChT and RT from January 2012 to December 2017. Totally 249 patients were identified that met inclusion criteria and of those 117 patients had sufficient tissue for PD-L1 immunohistochemical staining. Results Eighty patients (68.4%) expressed PD-L1 of ≥ 1% and 29.9% of more than 50%. Median PFS was 15.9 months in PD-L1 negative patients and 16.1 months in patients with PD-L1 expression ≥ 1% (p = 0.696). Median OS in PD-L1 negative patients was 29.9 months compared to 28.5 months in patients with PD-L1 expression ≥ % (p = 0.888). There was no difference in median OS in patients with high PD-L1 expression (≥ 50%) with 29.8 months compared to 29.9 months in those with low (1–49%) or no PD-L1 expression (p = 0.694). We found that patients who received a total dose of 60 Gy or more had significantly better median OS (32 months vs. 17.5 months, p < 0.001) as well as patients with PS 0 (33.2 vs. 20.3 months, p = 0.005). Conclusions In our patients PD-L1 expression had no prognostic value regarding PFS and OS. Patients with good performance status and those who received a total radiation dose of more than 60 Gy had significantly better mOS.

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“… 9 – 13 Notably, the approximate prevalence rates of PD-L1 tumor proportion score (TPS) ⩾50% are 18–28%, and for TPS ⩾1%, 47–68%, among patients with advanced NSCLC Stage IIIB or IV, including those with or without EGFR mutations and ALK alterations. 14 – 16 …”

Section: Introductionmentioning

confidence: 99%

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50%

Freemantle

Wilson³

et al. 2022

Ther Adv Med Oncol

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Background: For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published in November 2010–2020. Methods: Relevant RCTs were identified by searching databases and conference proceedings as per ISPOR, NICE, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR) and safety/tolerability. Fixed-effect models were used due to limited evidence. Various sensitivity analyses were conducted to validate the base case analyses. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded because an incompatible PD-L1 assay (SP142) was used for patient selection. For first-line advanced NSCLC with PD-L1 ⩾50%, cemiplimab was associated with statistically significant improvements in PFS [HR (95% credible interval [CrI]): 0.65 (0.50–0.86), 1–12 months] and ORR [odds ratio (OR) (95% CrI): 1.64 (1.04–2.62)], and comparable OS [HR (95% CrI): 0.77 (0.54–1.10), 1–12 months] versus pembrolizumab. There was no evidence of differences between cemiplimab and pembrolizumab for Grade 3–5 adverse events (AEs) [OR (95% CrI): 1.47 (0.83–2.60)], immune-mediated AEs [1.75 (0.33–7.49)], and all-cause discontinuation due to AEs [1.21 (0.58–2.61)]. Conclusions: Considering the limitations of indirect treatment comparisons, in patients with advanced NSCLC and PD-L1 ⩾50%, cemiplimab monotherapy demonstrated significant improvements in PFS and ORR, comparable OS, and no evidence of differences in safety/tolerability versus pembrolizumab.

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Real-World Prevalence of PD-L1 Expression Among Tumor Samples From Patients With Non–Small-Cell Lung Cancer

Cited by 11 publications

References 14 publications

Phase 1, pharmacogenomic, dose‐expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1‐deficient non‐squamous non‐small cell lung cancer

Phase 1, pharmacogenomic, dose‐expansion study of pegargiminase plus pemetrexed and cisplatin in patients with ASS1‐deficient non‐squamous non‐small cell lung cancer

Prognostic value of PD-L1 expression in patients with unresectable stage III non-small cell lung cancer treated with chemoradiotherapy

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50%

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