The integration of systemic and tumor PD-L1 as a predictive biomarker of clinical outcomes in patients with advanced NSCLC treated with PD-(L)1blockade agents

Over the last decade, the immune checkpoint blockade targeting the programmed death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) axis has improved progression-free and overall survival of advanced non-small cell lung cancer (NSCLC) patients. PD-L1 tumor expression, along with tumor mutational burden, is currently being explored as a predictive biomarker for responses to immune checkpoint inhibitors (ICIs). However, lung cancer patients may have insufficient tumor tissue samples and the high bleeding risk often prevents additional biopsies and, as a consequence, immunohistological evaluation of PD-L1 expression. In addition, PD-L1 shows a dynamic expression profile and can be influenced by intratumoral heterogeneity as well as the immune cell infiltrate in the tumor and its microenvironment, influencing the response rate to PD-1/PD-L1 axis ICIs. Therefore, to identify subgroups of patients with advanced NSCLC that will most likely benefit from ICI therapies, molecular characterization of PD-L1 expression in circulating tumor cells (CTCs) might be supportive. In this review, we highlight the use of CTCs as a complementary diagnostic tool for PD-L1 expression analysis in advanced NSCLC patients. In addition, we examine technical issues of PD-L1 measurement in tissue as well as in CTCs.

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132PD Plasma concentrations of pemetrexed to predict clinical outcomes in patients with advanced NSCLC

Journal of Thoracic Oncology ◽

10.1016/s1556-0864(18)30407-6 ◽

2018 ◽

Vol 13 (4) ◽

pp. S76-S77

Author(s):

S. Visser ◽

S. Koolen ◽

P. de Bruijn ◽

R. Mathijssen ◽

B. Stricker ◽

...

Keyword(s):

Clinical Outcomes ◽

Advanced Nsclc ◽

Plasma Concentrations

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Clinical outcomes of pembrolizumab therapy in advanced‐ NSCLC patients with poor performance status (≥3) and high PD‐L1 expression ( TPS ≥50%): A case series

Thoracic Cancer ◽

10.1111/1759-7714.13713 ◽

2020 ◽

Vol 11 (12) ◽

pp. 3618-3621

Author(s):

Ryoko Inaba‐Higashiyama ◽

Tatsuya Yoshida ◽

Hitomi Jo ◽

Masayuki Shirasawa ◽

Noriko Motoi ◽

...

Keyword(s):

Clinical Outcomes ◽

Advanced Nsclc ◽

Performance Status ◽

Case Series ◽

Poor Performance ◽

Poor Performance Status ◽

Nsclc Patients

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Long-term clinical outcomes of ALK inhibitors in patients with ALK-positive advanced non-small cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20542 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20542-e20542

Author(s):

Haruyasu Murakami ◽

Akira Ono ◽

Kazuhisa Nakashima ◽

Shota Omori ◽

Kazushige Wakuda ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Clinical Outcomes ◽

Advanced Nsclc ◽

Small Cell ◽

Small Cell Lung ◽

Alk Inhibitors ◽

Alk Inhibitor ◽

Alk Positive

e20542 Background: Anaplastic lymphoma kinase (ALK) inhibitors show high clinical efficacy in patients with ALK-positive advanced non-small cell lung cancer (NSCLC). However, the long-term clinical outcomes remain unknown. Methods: We retrospectively reviewed medical records of patients with ALK inhibitor-naïve ALK-positive advanced NSCLC who initiated alectinib or crizotinib therapy at the Shizuoka Cancer Center between June 2010 and December 2011. Results: This retrospective study included 14 patients (male/female, 5/9; PS 0/1, 6/8; adenocarcinoma/adenosquamous carcinoma, 13/1; smoker/never smoker, 8/6; brain metastasis presence/absence, 5/9; number of prior chemotherapy regimens 0/1/≥2, 1/7/6; alectinib/crizotinib, 4/10) with a median age of 55 years (range, 28-71). At the data cut-off (January 16, 2017), three patients were still receiving first ALK inhibitors (alectinib in two patients and crizotinib in one). One patient requested the discontinuation of alectinib therapy after five years. One patient discontinued crizotinib therapy due to unacceptable toxicity. Nine patients discontinued first ALK inhibitors due to disease progression. The overall response rate was 78.6% with complete response in two patients (14.3%), partial response in nine (64.3%), stable disease in one (7.1%), and progressive disease in two (14.3%). The median progression-free survival (PFS) for all 14 patients was 15.3 months, and the five-year PFS rate was 35.7%. The five-year PFS rates in patients treated with alectinib and crizotinib were 75.0% and 20.0%, respectively. The median overall survival (OS) for all 14 patients was 36.8 months, and the five-year OS rate was 42.9%. The five-year OS rates in patients treated with alectinib and crizotinib were 75.0% and 30.0%, respectively. Conclusions: ALK inhibitors showed favorable long-term clinical outcomes in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC, especially in patients treated with alectinib.

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Clinical outcomes of EGFR exon 20 insertion in advanced NSCLC in Korea.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e21136 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e21136-e21136

Author(s):

Seonggyu Byeon ◽

Youjin Kim ◽

Jiyun Lee ◽

Jong-Mu Sun ◽

Yoon-La Choi ◽

...

Keyword(s):

Clinical Outcomes ◽

Advanced Nsclc ◽

Exon 20

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Physiologic colonic uptake of 18F-FDG on PET/CT predicts immunotherapy response and gut microbiome diversity in patients with advanced non-small cell lung cancer (NSCLC).

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.9600 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 9600-9600

Author(s):

Lena Cvetkovic ◽

Claudine Régis ◽

Valerio Iebba ◽

Lisa Derosa ◽

Antoine Leblond ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Clinical Outcomes ◽

Gut Microbiome ◽

Advanced Nsclc ◽

Surrogate Marker ◽

Small Cell ◽

High Uptake ◽

Small Cell Lung ◽

Pet Ct

9600 Background: Immune checkpoint inhibitors (ICI) represent the backbone treatment of advanced non-small cell lung cancer (aNSCLC) patients. Emerging evidence suggests increased gut microbiome (GM) diversity is associated with favorable response. Conversely, antibiotic-induced dysbiosis may be associated with deleterious outcomes in patients receiving ICI in multiple retrospective studies and one prospective study. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics and could be a surrogate marker for GM diversity and therefore clinical response. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with outcomes and GM metagenomics in patients with advanced NSCLC. Methods: 71 patients with aNSCLC who underwent PET/CT prior to ICI were identified. For each patient, the colon was manually contoured, SUVmax was measured in each segment of the colon by a nuclear medicine specialist and average SUVmax was calculated for the whole colon. Patients were stratified in two groups according to median colon SUVmax (low vs high uptake). 18F-FDG physiologic colonic uptake was then compared to overall survival (OS), objective response (ORR), and progression-free survival (PFS). For patients with available stool samples (n = 10), GM composition was defined using metagenomics sequencing. Results: 71 patients (54% men, median age: 68 years) with aNSCLC were included in the study and ICI was the first line of therapy in 38% of those patients. The mean colon SUV for the low and high uptake groups were 1.41 (CI 95% 1.35-1.47) and 2.18 (CI 95% 1.90-2.46) respectively. The high uptake group had a higher proportion of non-responders (p = 0.033) and significant shorter PFS (4.1 months vs 11.3 months, p = 0.005). In the caecum, high uptake also correlated with numerically shorter OS (10.82 vs 27.56 months, p = 0.058) compared to low uptake group. Despite the low number of samples, metagenomics sequencing revealed that PLS-DA (Partial Least Squares Discriminant Analysis) for diversity was lower in the high SUV group (p = 0.008). Conclusions: Higher colon SUVmax on pre-ICI FDG PET/CT is associated with worse clinical outcomes and lower baseline GM diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a surrogate marker of GM diversity and predicts clinical outcomes.

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P1.07-024 ISEND May Predict Clinical Outcomes for Advanced NSCLC Patients on PD-1/PD-L1 Inhibitors but Not Chemotherapies or Targeted Kinase Inhibitors

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2017.09.942 ◽

2017 ◽

Vol 12 (11) ◽

pp. S2005

Author(s):

W. Park ◽

D. Kwon ◽

A. Desai ◽

V. Florou ◽

D. Saravia ◽

...

Keyword(s):

Clinical Outcomes ◽

Kinase Inhibitors ◽

Advanced Nsclc ◽

Nsclc Patients

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Immune-Related Adverse Events Are Associated With Clinical Benefit in Patients With Non-Small-Cell Lung Cancer Treated With Immunotherapy Plus Chemotherapy: A Retrospective Study

Frontiers in Oncology ◽

10.3389/fonc.2021.630136 ◽

2021 ◽

Vol 11 ◽

Author(s):

Kenji Morimoto ◽

Tadaaki Yamada ◽

Chieko Takumi ◽

Yuri Ogura ◽

Takayuki Takeda ◽

...

Keyword(s):

Lung Cancer ◽

Adverse Events ◽

Confidence Interval ◽

Small Cell Lung Cancer ◽

Clinical Outcomes ◽

Cell Lung Cancer ◽

Advanced Nsclc ◽

Small Cell ◽

Hazard Ratio ◽

Small Cell Lung

BackgroundThe immunotherapy plus chemotherapy combination is one of the most promising treatments in advanced non-small-cell lung cancer (NSCLC). Immunotherapy often causes immune-related adverse events (irAEs), which have been reported to be associated with the good clinical outcomes. However, the effects of immunotherapy plus chemotherapy remain unknown. In this study, we investigated the association between irAEs caused by immunotherapy plus chemotherapy and clinical efficacy in patients with advanced NSCLC.Materials and MethodsWe retrospectively analyzed the data of patients with advanced NSCLC, who received a combination of immunotherapy plus chemotherapy at six institutions in Japan between January 2019 and September 2019. We examined the effect of irAEs on various clinical outcomes.ResultsWe included 70 patients with advanced NSCLC. Patients were divided into two groups: patients with irAEs and patients without irAEs. Patients with irAEs had significantly longer progression-free survival than those without irAEs on univariate (hazard ratio 0.53, 95% confidence interval 0.30–0.93, p = 0.026) and multivariate (hazard ratio 0.53, 95% confidence interval 0.29–0.97, p = 0.041) analyses. In addition, patients with grade 1–2 irAEs (mild irAEs) had significantly longer progression-free and overall survival than those with grade 3-5 irAEs (severe irAEs) or without irAEs on univariate (398 days versus 189 days, respectively; p = 0.0061) and multivariate (not reached versus 412 days, respectively; p = 0.021) analyses.ConclusionPatients with NSCLC who experienced mild irAEs showed better response to treatment with immunotherapy plus chemotherapy than those with severe irAEs or without irAEs. Further large-scale research is warranted to confirm these findings.

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