Predictive Factors for Poor Progression-free Survival in Patients with Non-small Cell Lung Cancer Treated with Nivolumab

Taniguchi, Yoshihiko; Tamiya, Akihiro; Isa, Syun-Ichi; Nakahama, Kenji; Okishio, Kyoichi; Shiroyama, Takayuki; Suzuki, Hidekazu; Inoue, Tomio; Tamiya, Motohiro; Hirashima, Tomonori; Imamura, Fumio; Atagi, Shinji

doi:10.21873/anticanres.12030

Cited by 43 publications

(36 citation statements)

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“…Patients were stratified as low-and high-NLR (< 5 and ≥ 5, respectively) [10], low-and high-LDH (< 240 and ≥ 240 U/L) [12], or low-and high-PNI (< 45 and ≥ 45) groups [21]. These cutoffs were selected according to literature references 10, 12, 21 and their median, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…LDH was found associated with outcomes in melanoma patients treated with immune checkpoint inhibitors [32,33]. Several studies used LDH to forecast PFS [12,34] and OS [6,11] in patients with NSCLC treated with immune checkpoint inhibitors. Taniguchi et al [12] discovered that among patients with advanced NSCLC treated with nivolumab, those with baseline LDH > 240 U/L had a significantly worse PFS compared with those with LDH ≤ 240 U/L.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies used LDH to forecast PFS [12,34] and OS [6,11] in patients with NSCLC treated with immune checkpoint inhibitors. Taniguchi et al [12] discovered that among patients with advanced NSCLC treated with nivolumab, those with baseline LDH > 240 U/L had a significantly worse PFS compared with those with LDH ≤ 240 U/L. Similarly, the present analysis showed that a baseline LDH ≥ 240 U/L was associated with worse OS and PFS.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, a high pretreatment NLR is putatively a poor prognostic indicator in NSCLC [8][9][10]. So too, high serum LDH is reportedly a risk factor of poor prognosis in patients with NSCLC [11][12][13].…”

Section: Introductionmentioning

confidence: 98%

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Peripheral blood markers predictive of outcome and immune-related adverse events in advanced non-small cell lung cancer treated with PD-1 inhibitors

Peng

Wang

Liu

et al. 2020

Cancer Immunol Immunother

145

122

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Background Selected patients with advanced non-small cell lung cancer (NSCLC) benefit from immunotherapy, especially immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1) inhibitor. Peripheral blood biomarkers would be most convenient to predict treatment outcome and immune-related adverse events (irAEs) in candidate patients. This study explored associations between inflammation-related peripheral blood markers and onset of irAEs and outcome in patients with advanced NSCLC receiving PD-1 inhibitors. Methods A retrospective analysis was conducted of 102 patients with advanced NSCLC receiving PD-1 inhibitors from January 2017 to May 2019. Cox regression models were employed to assess the prognostic effect of low/high neutrophil/ lymphocyte ratio (NLR), lactate dehydrogenase (LDH), and prognostic nutrition index (PNI) on overall survival (OS) and progression-free survival (PFS). Logistic regression models were used to analyze the correlation between peripheral blood markers and the onset of irAEs. Result NLR < 5, LDH < 240 U/L, or PNI ≥ 45 was favorably associated with significantly better outcomes compared with higher, higher, or lower values, respectively. The multivariate analysis determined that these parameters were independently associated with both better PFS (p = 0.049, 0.046, 0.014, respectively) and longer OS (p = 0.007, 0.031, < 0.001, respectively). Patients with three favorable factors among NLR, LDH, and PNI had better PFS and OS than did those with two, one, or none. PNI and NLR were associated with the onset of irAEs. Conclusion In patients with advanced NSCLC treated with PD-1 inhibitors, pretreatment NLR, LDH, and PNI may be useful predictive markers of clinical outcome and irAEs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 2 more Smart Citations

Peripheral blood markers predictive of outcome and immune-related adverse events in advanced non-small cell lung cancer treated with PD-1 inhibitors

Peng

Wang

Liu

et al. 2020

Cancer Immunol Immunother

145

122

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“…However, patients with advanced lung cancer have 10-15% overall 5-year survival rates, an median overall survival (OS) of about 11.1 months, and a post-recurrence survival rate (PRS) of 13% (hazard ratio (HR) = 0.78) [2][3][4]. Even with second-line drug treatment, such as nivolumab, progression-free survival (PFS) is about 2.3-3.5 months [5]. It is therefore critical to elucidate the molecular mechanisms of lung cancer proliferation and metastasis to identify and develop novel therapeutic targets in lung cancer.…”

Section: Introductionmentioning

confidence: 99%

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

Chang

Hsiao

et al. 2019

Cancers

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Dysregulation of forkhead box D1 (FOXD1) is known to promote tumor progression; however, its molecular mechanism of action is unclear. Based on microarray analysis, we identified galectin-3/LGALS3 (Gal-3) as a potential downstream target of FOXD1, as FOXD1 transactivated Gal-3 by interacting with the Gal-3 promoter to upregulate Gal-3 in FOXD1-overexpressing CL1-0 lung cancer cells. Ectopic expression of FOXD1 increased the expression of Gal-3 and the growth and motility of lung cancer cells, whereas depletion of Gal-3 attenuated FOXD1-mediated tumorigenesis. ERK1/2 interacted with FOXD1 in the cytosol and translocated FOXD1 into the nucleus to activate Gal-3. Gal-3 in turn upregulated FOXD1 via the transcription factor proto-oncogene 1 (ETS-1) to transactivate FOXD1. The increase in ETS-1/FOXD1 expression by Gal-3 was through Gal-3-mediated integrin-β1 (ITGβ1) signaling. The overexpression of both FOXD1 and Gal-3 form a positive regulatory loop to promote lung cancer aggressiveness. Moreover, both FOXD1 and Gal-3 were positively correlated in human lung cancer tissues. Our findings demonstrated that FOXD1 and Gal-3 form a positive feedback loop in lung cancer, and interference of this loop may serve as an effective therapeutic target for the treatment of lung cancers, particularly those related to dysregulation of Gal-3.

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Pre‐ and on‐treatment lactate dehydrogenase as a prognostic and predictive biomarker in advanced non–small cell lung cancer

Tjokrowidjaja

Lord

John

et al. 2022

Cancer

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BACKGROUND:The survival outcomes of patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are variable. This study investigated whether pre-and on-treatment lactate dehydrogenase (LDH) could better prognosticate and select patients for ICI therapy. METHODS: Using data from the POPLAR and OAK trials of atezolizumab versus docetaxel in previously treated advanced NSCLC, the authors assessed the prognostic and predictive value of pretreatment LDH (less than or equal to vs greater than the upper limit of normal). They further examined changes in on-treatment LDH by performing landmark analyses and estimated overall survival (OS) distributions according to the LDH level stratified by the response category (complete response [CR]/ partial response [PR] vs stable disease [SD]). They repeated pretreatment analyses in subgroups defined by the programmed death ligand 1 (PD-L1) status. RESULTS: This study included 1327 patients with available pretreatment LDH. Elevated pretreatment LDH was associated with an adverse prognosis regardless of treatment (hazard ratio [HR] for atezolizumab OS, 1.49; P = .0001; HR for docetaxel OS, 1.30; P = .004; P for treatment by LDH interaction = .28). Findings for elevated pretreatment LDH were similar for patients with positive PD-L1 expression treated with atezolizumab. Persistently elevated on-treatment LDH was associated with a 1.3-to 2.8-fold increased risk of death at weeks 6, 12, 18, and 24 regardless of treatment. Elevated LDH at 6 weeks was associated with significantly shorter OS regardless of radiological response (HR for CR/PR, 2.10; P = .04; HR for SD, 1.50; P < .01), with similar findings observed at 12 weeks. CONCLUSIONS: In previously treated advanced NSCLC, elevated pretreatment LDH is an independent adverse prognostic marker. There is no evidence that pretreatment LDH predicts ICI benefit. Persistently elevated on-treatment LDH is associated with worse OS despite radiologic response.

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Predictive Factors for Poor Progression-free Survival in Patients with Non-small Cell Lung Cancer Treated with Nivolumab

Abstract: PS score ≥2, steroid use at baseline and a high LDH level were predictive of poor PFS in patients with NSCLC treated with nivolumab. Careful monitoring is recommended for treating such patients with nivolumab (UMIN-ID: UMIN000025908).

Cited by 43 publications

References 0 publications

Peripheral blood markers predictive of outcome and immune-related adverse events in advanced non-small cell lung cancer treated with PD-1 inhibitors

Peripheral blood markers predictive of outcome and immune-related adverse events in advanced non-small cell lung cancer treated with PD-1 inhibitors

FOXD1 and Gal-3 Form a Positive Regulatory Loop to Regulate Lung Cancer Aggressiveness

Pre‐ and on‐treatment lactate dehydrogenase as a prognostic and predictive biomarker in advanced non–small cell lung cancer

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