Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer: a prospective observational study

Yoshimura, Akihiro; Yamada, Tadaaki; Okuma, Yusuke; Fukuda, Akito; Watanabe, Satoshi; Nishioka, Naoya; Takeda, Takayuki; Chihara, Yusuke; Takemoto, Shinnosuke; Harada, Taishi; Hiranuma, Osamu; Shirai, Yukina; Nishiyama, Akihiro; Yano, Seiji; Gotô, Yasuhiro; Shiotsu, Shinsuke; Kunimasa, Kei; Morimoto, Yoshie; Iwasaku, Masahiro; Kaneko, Yoshiko; Uchino, Junichi; Kenmotsu, Hirotsugu; Takahashi, Toshiaki; Takayama, K.

doi:10.21037/tlcr-21-461

Cited by 16 publications

(21 citation statements)

References 48 publications

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“…Previous studies have reported PD-L1 TPS <1% in 42.4%-62.7%, 1%-49% in 25.55%-37.6%, and ≥ 50% in 9.4%-21.2% of lung adenocarcinoma patients. 15,23,33 PD-L1 TPS in this study was 49.2% for <1%, 29.5% for 1%-49%, and 21.3% for ≥50%, similar to previously reported results.…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies have reported PD‐L1 TPS <1% in 42.4%–62.7%, 1%–49% in 25.55%–37.6%, and ≥ 50% in 9.4%–21.2% of lung adenocarcinoma patients. 15 , 23 , 33 PD‐L1 TPS in this study was 49.2% for <1%, 29.5% for 1%–49%, and 21.3% for ≥50%, similar to previously reported results. The association between PD‐L1 TPS and therapeutic efficacy of first/second generation EGFR‐TKIs have been reported in many studies, with patients with PD‐L1 TPS ≥50% reported to have lower objective response rate, shorter PFS, and more de novo resistance compared to those with TPS < 50%.…”

Section: Discussionsupporting

confidence: 92%

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Retrospective analysis of independent predictors of progression‐free survival in patients with EGFR mutation‐positive advanced non‐small cell lung cancer receiving first‐line osimertinib

et al. 2022

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Background: Clinically measurable factors affecting the progression-free survival (PFS) of patients receiving osimertinib as first-line therapy for epidermal growth factor receptor (EGFR) mutation-positive advanced non-small cell lung cancer (NSCLC)have not yet been established. Methods: We retrospectively reviewed the medical records of 61 patients treated with osimertinib as primary therapy for EGFR mutation-positive advanced NSCLC at Yokohama City University Medical Center between August 2018 and March 2022. Our objective was to identify the independent predictors of PFS. Results: The median age of participants was 74 years. Overall, 73.8% had good (0-1) Eastern Cooperative Oncology Group performance status (PS), and 98.4% had histology of adenocarcinoma. The EGFR mutation was exon19 deletion in 52.5% and exon21 L858R in 44.3% of patients. Programmed death-ligand 1 tumor proportion score >50% was observed in 21.3% and liver metastasis in 9.9% of patients. Median PFS was 19.5 months (95% confidence interval [CI]: 10.6-31.6), and overall survival was not reached. The objective response rate was 68.9%, and disease control rate was 93.4%. Multivariate analysis showed that poor PS (2-4) negatively impacted PFS (hazard ratio, 3.79; 95% CI: 1.46-9.87; p = 0.006). Median PFS in the good PS and poor PS groups was 20.4 months (95% CI: 12.4-not evaluable) and 7.2 months (95% CI: 7.2-19.5), respectively. Interstitial lung disease of all grades and grade 3 was observed as an adverse event in 6.6 and 4.9% of patients, respectively. Conclusion: Poor PS was associated with poor prognosis in patients with EGFR mutation-positive advanced NSCLC treated with osimertinib as first-line therapy.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Retrospective analysis of independent predictors of progression‐free survival in patients with EGFR mutation‐positive advanced non‐small cell lung cancer receiving first‐line osimertinib

et al. 2022

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“…Several previous studies showed that EGFR-mutated advanced NSCLC with high TPS had poorer treatment outcomes with first-or second-generation EGFR-TKI compared with the weak or negative PD-L1 population [12,13]. Regarding osimertinib, a recent study of 71 patients who received first-line osimertinib revealed that patients with ind PD-L1 expression had poorer PFS than those with low or negative PD-L1 (median PFS, 5.0 vs. 17.4 months, p < 0.001) [14]. The present study demonstrated similar results in a larger sample size.…”

Section: Discussionmentioning

confidence: 99%

Outcomes of first-line osimertinib treatment for epidermal growth factor receptor-mutated non-small cell lung cancer in clinical practice settings

Shiozawa

Numata

Tamura

et al. 2022

Preprint

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Background: Real-world data on the clinical outcomes of first-line osimertinib treatment for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations is lacking. This study aimed to evaluate the treatment outcomes and the prognostic factors of osimertinib as first-line therapy in clinical practice settings.Methods: We retrospectively evaluated clinical outcomes of patients with EGFR-mutated NSCLC treated with osimertinib as first-line therapy across 12 institutions in Japan between August 2018 and March 2020.Results: Among 158 enrolled patients, the objective response rate (ORR) was 68% and the estimated median progression-free survival (PFS) was 17.1 months (95% confidence interval [CI], 14.5-19.7). Subgroup analysis showed that PFS in the group with high programmed death-ligand 1 (PD-L1) expression was significantly shorter than that in groups with low or no PD-L1 expression (10.1 vs. 16.1 vs. 19.0 months; p = 0.03). Univariate and multivariate analyses demonstrated that high PD-L1 expression was the only independent adverse prognostic factor of osimertinib outcome for PFS (hazard ratio, 2.71; 95% CI: 1.26-5.84; p = 0.01). In terms of the ORR, there was no statistically significant difference regardless of PD-L1 expression (67% vs. 76% vs. 65%; p = 0.51).Conclusion: Osimertinib showed favorable treatment outcomes in clinical practice. Although the ORR was similar regardless of PD-L1 expression, high PD-L1 expression could be an independent adverse prognostic factor related to PFS in osimertinib treatment.

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“…In contrast, immune‐checkpoint inhibitors (ICIs) are generally less effective in NSCLC patients harboring driver mutations, such as EGFR and ALK 22,23 . Elevated PD‐L1 expression in tumors is reportedly a negative predictive factor for EGFR‐TKI outcomes in NSCLC patients with EGFR mutations 24–26 …”

Section: Introductionmentioning

confidence: 99%

“… 22 , 23 Elevated PD‐L1 expression in tumors is reportedly a negative predictive factor for EGFR‐TKI outcomes in NSCLC patients with EGFR mutations. 24 , 25 , 26 …”

Section: Introductionmentioning

confidence: 99%

High levels of AXL expression in untreated EGFR‐mutated non‐small cell lung cancer negatively impacts the use of osimertinib

et al. 2022

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For non‐small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, the initial therapeutic interventions will have crucial impacts on their clinical outcomes. Drug tolerant factors reportedly have an impact on EGFR‐tyrosine kinase inhibitor sensitivity. This prospective study investigated the impacts of drug tolerant‐related protein expression in tumors based on the efficacy of osimertinib in the first‐setting of EGFR‐mutated advanced NSCLC patients. A total of 92 patients with EGFR‐mutated advanced or postoperative recurrent NSCLC were analyzed and treated with osimertinib at 14 institutions in Japan. AXL, p53, and programmed death‐ligand 1 (PD‐L1) expression in patient tumors was determined using immunohistochemistry. The AXL signaling pathway was investigated using a cell line‐based assay and AXL‐related gene expression in The Cancer Genome Atlas (TCGA) database. High levels of AXL and positive‐p53 expression were detected in 26.1% and 53.3% of the pretreatment EGFR‐mutated NSCLC tumors, respectively. High AXL expression levels were significantly associated with a shorter progression‐free survival compared with low AXL expression levels, irrespective of the EGFR activating mutation status (p = 0.026). Cell line‐based assays indicated that the overexpression of AXL protein accelerated PD‐L1 expression, which induced insensitivity to osimertinib. In the TCGA database, AXL RNA levels were positively correlated with PD‐L1 expression in the lung adenocarcinoma cohort. The results show that high AXL expression levels in tumors impact clinical predictions when using osimertinib to treat EGFR‐mutated NSCLC patients. Trial Registration: UMIN000043942.

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Impact of tumor programmed death ligand-1 expression on osimertinib efficacy in untreated EGFR-mutated advanced non-small cell lung cancer: a prospective observational study

Cited by 16 publications

References 48 publications

Retrospective analysis of independent predictors of progression‐free survival in patients with EGFR mutation‐positive advanced non‐small cell lung cancer receiving first‐line osimertinib

Retrospective analysis of independent predictors of progression‐free survival in patients with EGFR mutation‐positive advanced non‐small cell lung cancer receiving first‐line osimertinib

Outcomes of first-line osimertinib treatment for epidermal growth factor receptor-mutated non-small cell lung cancer in clinical practice settings

High levels of AXL expression in untreated EGFR‐mutated non‐small cell lung cancer negatively impacts the use of osimertinib

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