Different prognostic implications of hepatic metastasis according to front-line treatment in non-small cell lung cancer: a real-world retrospective study

Although osimertinib is the standard-of-care treatment of epidermal growth factor receptor (EGFR) T790M mutation-positive non-small cell lung cancer, real-world evidence on the efficacy of osimertinib is not enough to reflect the complexity of the entire course of treatment.Herein, we report on the use of osimertinib in patients with EGFR T790M mutation-positive non-small cell lung cancer who had previously received EGFR tyrosine kinase inhibitor (TKI) treatment in Korea. Materials and MethodsPatients with confirmed EGFR T790M after disease progression of prior EGFR-TKI were enrolled and administered osimertinib 80 mg daily. The primary effectiveness outcome was progression-free survival, with time-to-treatment discontinuation, treatment and adverse effects leading to treatment discontinuation, and overall survival being the secondary endpoints. ResultsA total of 558 individuals were enrolled, and 55.2% had investigator-assessed responses. The median progression-free survival was 14.2 months (95% confidence interval (CI), 13.0-16.4), and the median time-to-treatment discontinuation was 15.0 months (95% CI, 14.1-15.9). The median overall survival was 36.7 months (95% CI, 30.9-not reached). The benefit with osimertinib was consistent regardless of the age, sex, smoking history, and primary EGFR mutation subtype. However, hepatic metastases at the time of diagnosis, the presence of plasma EGFR T790M, and the shorter duration of prior EGFR-TKI treatment were poor predictors of osimertinib treatment. Ten (1.8%) patients, including three with pneumonitis, had to discontinue osimertinib due to severe adverse effects. ConclusionOsimertinib demonstrated its clinical effectiveness and survival benefit for EGFR T790M mutation-positive in Korean patients with no new safety signals.

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“…Hepatic metastasis has been known to be an independent poor prognostic factor in EGFRmutant NSCLC patients receiving EGFR-TKI [20].…”

Section: A C C E P T E D a R T I C L E Korean Cancer Associationmentioning

confidence: 99%

Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer

et al. 2023

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“…Previous studies reported that NSCLC patients with liver metastases have a poor prognosis. [42][43][44] However, the number of cases with liver metastasis in the present study was small, and our findings need to be confirmed using a larger sample. Moreover, the presence of driver gene mutation/translocation was statistically significant for PPS in the univariate analysis but not in the multivariate analysis.…”

mentioning

confidence: 55%

Clinical impact of post-progression survival in patients with locally advanced non-small cell lung cancer after chemoradiotherapy

Imai

Kobayashi

Kaira

et al. 2022

Radiology and Oncology

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Background The efficacy of first-line chemoradiotherapy for overall survival (OS) might be confounded by the subsequent treatments in patients with locally advanced non-small cell lung cancer (NSCLC). In this study, we assessed the associations of progression-free survival (PFS) and post-progression survival (PPS) with OS after chemoradiotherapy for locally advanced NSCLC using patient-level data. Patients and methods Between January 2011 and December 2018, 45 patients with locally advanced NSCLC who had received first-line chemoradiotherapy and in whom recurrence occurred were analysed. The associations of PFS and PPS with OS were analysed at the individual level. Results Linear regression and Spearman rank correlation analyses revealed that PPS was strongly correlated with OS (r = 0.72, p < 0.05, R2 = 0.54), whereas PFS was moderately correlated with OS (r = 0.58, p < 0.05, R 2 = 0.34). The Glasgow prognostic score and liver metastases at recurrence were significantly associated with PPS (p < 0.001). Conclusions The current analysis of individual-level data of patients treated with first-line chemoradiotherapy implied that PPS had a higher impact on OS than PFS in patients with locally advanced NSCLC. Additionally, current perceptions indicate that treatment beyond progression after first-line chemoradiotherapy might strongly affect OS.

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“…Other studies did not find significant difference in ICI efficacy between NSCLC patients with liver metastasis and without. A real-world study which included 1470 patients but only contained 11 patients with liver metastasis found that PFS ( p = 0.955) and OS ( p = 0.968) were similar in liver metastasis patients or non-liver metastasis patients in treating with ICIs [ 11 ]. Immunochemotherapy was equally effective in lung cancer patients with or without liver metastasis (the HR of PFS: 1.11, 95%CI: 0.92–1.34; the HR of OS: 1.03, 95%CI: 0.80–1.35) from a meta-analysis [ 12 ].…”

Section: Discussionmentioning

confidence: 99%

“…A subgroup analysis in several phase III clinical studies has shown that NSCLC patients with liver metastases can benefit from ICI therapy [ 3 , 4 ]. In addition, other studies have reported that the efficacy of ICIs in NSCLC patients with liver metastases is similar to that in patients without liver metastases [ 11 , 12 ]. Conversely, several studies have drawn different conclusions, suggesting that ICI has limited efficiency in NSCLC patients who have liver metastasis.…”

Section: Introductionmentioning

confidence: 98%

The Efficacy of PD-1/PD-L1 Inhibitors in Patients with Liver Metastasis of Non-Small Cell Lung Cancer: A Real-World Study

Xie

et al. 2022

Cancers

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Background: A controversy exists regarding the efficacy of programmed death-1 (PD-1)/ programmed death ligand-1 (PD-L1) inhibitors for patients with non-small cell lung cancer (NSCLC) and liver metastases. Our study retrospectively evaluated the efficacy of PD-1/PD-L1 inhibitors in NSCLC patients with liver metastases. Methods: This retrospective study included 1627 lung cancer patients who received immunotherapy. Among 648 patients who had advanced NSCLC and received PD-1/PD-L1 inhibitors, 61 had liver metastases and 587 did not have. We analyzed patient characteristics, progression-free survival (PFS) and overall survival (OS). An exploratory analysis of biomarkers including CD4, CD8 and CD68 for efficacy in patients with liver metastases was also performed. Results: In liver metastasis patients receiving PD-1/PD-L1 inhibitors, the objective response rate (ORR) was 29.5%, the disease control rate (DCR) was 72.1%, PFS was 6.4 months and OS was 15.2 months, which were all worse than those of patients without liver metastases (ORR: 35.8%; DCR: 81.8%; PFS: 7.9 months, p = 0.001; OS: 20.6 months, p = 0.008). When compared to non-liver lesions, the ORR (26.2 vs. 39.3%) and DCR (75.4 vs. 88.5%) of liver lesions were lower. During the analysis of PD-L1 expression, 27 PD-L1-positive patients had a longer PFS than 21 patients in the negative group (p = 0.012). Being PD-L1 positive was the independent prognostic indicators for PFS (p = 0.006). Additionally, the PD-L1 and CD8 dual-positive group responded favorably to PD-1/PD-L1 inhibitors. Conclusions: PD-1/PD-L1 inhibitors are effective in liver metastasis–NSCLC patients. However, the efficacy is inferior when compared to those of patients without liver metastases. In NSCLC patients with liver metastases, PD-L1 expression and CD8+ T cell infiltration can predict the response of PD-1/PD-L1-directed immunotherapy.

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Different prognostic implications of hepatic metastasis according to front-line treatment in non-small cell lung cancer: a real-world retrospective study

Cited by 15 publications

References 32 publications

Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer

Real-World Study of Osimertinib in Korean Patients with Epidermal Growth Factor Receptor T790M Mutation–Positive Non–Small Cell Lung Cancer

Clinical impact of post-progression survival in patients with locally advanced non-small cell lung cancer after chemoradiotherapy

The Efficacy of PD-1/PD-L1 Inhibitors in Patients with Liver Metastasis of Non-Small Cell Lung Cancer: A Real-World Study

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