Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation–positive non–small-cell lung cancer in a real-world setting (OSI-FACT)

Sakata, Yoshihiko; Sakata, Shinya; Oya, Yuko; Tamiya, Motohiro; Suzuki, Hidekazu; Shibaki, Ryota; Okada, Asuka; Kobe, Hiroshi; Matsumoto, Hirotaka; Yokoi, Takashi; Sato, Yuki; Uenami, Takeshi; Saito, Go; Tsukita, Yoko; Inaba, Megumi; Ikeda, Hideki; Arai, Daisuke; Maruyama, Hirotaka; Hara, Satoshi; Tsumura, Shinsuke; Morinaga, Jun; Sakagami, Takuro

doi:10.1016/j.ejca.2021.09.041

Cited by 48 publications

(51 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, our study showed remarkably lower efficacy of osimertinib as well as other EGFR-TKIs in patients with liver metastasis. Moreover, the same trend was observed in another retrospective study [ 24 ], suggesting that the clinical efficacy of any EGFR-TKI monotherapy is limited to NSCLC with liver metastasis. In the tumor microenvironment of the liver metastatic site, the expression level of vascular endothelial growth factor (VEGF) is increased in comparison with other metastatic sites [ 25 ].…”

Section: Discussionsupporting

confidence: 78%

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

et al. 2022

View full text Add to dashboard Cite

Background Osimertinib—the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)—has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs. Methods Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n = 183), afatinib (n = 55), or osimertinib (n = 150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR). Results In univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs. Conclusion Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.

show abstract

Section: Discussionsupporting

confidence: 78%

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

et al. 2022

View full text Add to dashboard Cite

show abstract

“…However, our study showed remarkably lower e cacy of osimertinib as well as other EGFR-TKIs in patients with liver metastasis. Moreover, the same trend was observed in another retrospective study [24], suggesting that the clinical e cacy of any EGFR-TKI monotherapy is limited to NSCLC with liver metastasis. In the tumor microenvironment of the liver metastatic site, the expression level of vascular endothelial growth factor (VEGF) is increased in comparison with other metastatic sites [25].…”

Section: Discussionsupporting

confidence: 76%

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

Sobue

Tanaka

Morise

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Osimertinib—the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)—has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs.Methods: Clinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n=183), afatinib (n=55), or osimertinib (n=150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR).Results: In univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs.Conclusion: Osimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.

show abstract

“…In studies that scored clinical factors and created nomograms to predict PFS for first/second generation EGFR‐TKIs, PS was reported as an essential predictor of PFS 14 . However, in the few real‐world studies on first‐line osimertinib therapy, PS is not listed as an independent predictor of PFS, 21,22 but the results of this study suggest that PS is an independent predictor of PFS for first‐line osimertinib. Currently, in Japan, gefitinib or erlotinib, first‐generation EGFR‐TKIs, are recommended as first‐line treatment for patients with EGFRm+ advanced NSCLC and a PS of 2, while gefitinib is preferred in patients with a PS of 3–4, based on the evidence of safety and efficacy 5,28–30 .…”

Section: Discussionmentioning

confidence: 59%

“…[15][16][17][18] There are few reports on the association between PD-L1 TPS and treatment response to osimertinib, but as with first/second generation EGFR-TKIs, patients with PD-L1 TPS ≥50% have been reported to have a shorter PFS compared to those with TPS < 50%. 21,23 In a subset analysis of the FLAURA trial, median PFS was 18.9 months (95% CI: 12.4-noncalculable) for PD-L1 TPS <1% and 18.4 months (95% CI: 10.9-noncalculable) for PD-L1 TPS ≥1%, suggesting that PFS is not affected by PD-L1 TPS. 20 However, only 3.6% of the FLAURA study participants had PD-L1 TPS ≥50%, which deviates from the real-world data.…”

Section: Discussionmentioning

confidence: 99%

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

View full text Add to dashboard Cite

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.

show abstract

Osimertinib as first-line treatment for advanced epidermal growth factor receptor mutation–positive non–small-cell lung cancer in a real-world setting (OSI-FACT)

Cited by 48 publications

References 26 publications

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

Clinical efficacy of osimertinib in EGFR-mutant non-small cell lung cancer with distant metastasis

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

Contact Info

Product

Resources

About