GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients

Peled, Nir; Gillis, Roni; Kılıçkap, Saadettin; Froesch, Patrizia; Орлов, С. В.; Филиппова, Е. А.; Demırcı, Umut; Christopoulos, Petros; Çiçin, İrfan; Başal, Fatma Buğdaycı; Yılmaz, Caner; Moiseenko, Fedor; Korkmaz, Taner; Paydaş, Semra; Gautschi, Oliver; Zırtıloğlu, Alişan; Eralp, Yeşim; Çınkır, Havva Yeşil; Sezer, Ahmet; Erman, Mustafa; Tural, Deniz; Turna, Hande; Dudnik, Elizabeth; Reguart, Noemı́; Camidge, D. Ross; Ng, Terry L.; Şenler, Filiz Çay; Beypınar, İsmail; Yazılıtaş, Doğan; Demirkazık, Ahmet; Karaoğlu, Aziz; Okutur, Kerem; Çoşkun, Hasan Şenol; Şendur, Mehmet Ali Nahit; Işıkdoğan, Abdurrahman; Çabuk, Devrim; Yumuk, Perran Fulden; Yıldız, İbrahim; Kaplan, Mehmet; Özyılkan, Özgür; Öztop, İlhan; Ölmez, Ömer Fatih; Aydın, Kübra; Aydıner, Adnan; Meydan, Nezih; Grinberg, R; Roisman, Laila C.

doi:10.1016/j.lungcan.2020.07.022

Cited by 24 publications

(10 citation statements)

References 28 publications

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“…In the past, patients with NSCLC with other target mutations had no relevant targeted drug options and were required to undergo treatment with conventional chemotherapy regimens. In recent years, with the development of molecular medicine, targeted drugs have become available for non-EGFR mutations, including anaplastic lymphoma kinase ( 3 ), c-ros oncogene 1 ( 4 ) and MET proto-oncogene ( 5 ) mutations. To date, three generations of EGFR inhibitors have been approved by the US Food and Drug Administration for the treatment of patients with NSCLC with EGFR-activating mutations or secondary T790M mutations.…”

Section: Introductionmentioning

confidence: 99%

Tumor‑associated macrophage‑derived exosomes promote EGFR‑TKI resistance in non‑small cell lung cancer by regulating the AKT, ERK1/2 and STAT3 signaling pathways

Yuan

Zheng

et al. 2022

Oncol Lett

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The evolutionary properties of organisms lead to the issue of targeted drug resistance. Numerous clinical trials have shown that tumor-associated macrophages (TAMs) in patients with lung cancer adversely affect the clinical efficacy of epithelial growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). However, the mechanism by which TAMs influence the tumor cell response to TKIs remains unclear. The aim of the present study was to investigate the influence of TAM-derived exosomes on the sensitivity of PC9 and HCC827 lung adenocarcinoma cells to the EGFR inhibitor gefitinib. Multiple cytokines were used to induce the differentiation of THP-1 human leukemia monocytes into macrophages in vitro. The obtained cells were identified as TAMs by cytomorphology and flow cytometry. Exosomes were extracted from the TAM culture supernatants and identified using electron microscopy and nanoparticle tracking analysis. Flow cytometry was used to examine the apoptosis of lung adenocarcinoma cells when treated with gefitinib and/or TAM-derived exosomes. In addition, western blotting was used to detect the expression of the key proteins of the AKT, ERK1/2 and STAT3 signaling pathways. TAM-derived exosomes were successfully obtained. The TAM-derived exosomes were shown to affect the proliferation and apoptosis of lung adenocarcinoma cells. Furthermore, the killing effect of gefitinib on the tumor cells was attenuated. The mechanism underlying the effects of the TAM-derived exosomes may be associated with reactivation of the AKT, ERK1/2 and STAT3 signaling pathways. In conclusion, the findings indicate that TAM-derived exosomes promote resistance to gefitinib in non-small cell lung cancer (NSCLC), and the mechanism may be associated with reactivation of the AKT, ERK1/2 and STAT3 signaling pathways. This study may serve as a reference in the exploration of alternative strategies for NSCLC following the development of resistance to EGFR-targeted drugs.

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Section: Introductionmentioning

confidence: 99%

Tumor‑associated macrophage‑derived exosomes promote EGFR‑TKI resistance in non‑small cell lung cancer by regulating the AKT, ERK1/2 and STAT3 signaling pathways

Yuan

Zheng

et al. 2022

Oncol Lett

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“…Thus, lorlatinib may be established as a good option in patients pre-treated with one or two ALK TKIs. Currently, the first real-world data confirm the meaningful results from the pivotal studies [ 57 , 58 ].…”

Section: Current Anaplastic Lymphoma Kinase (Alk) Tyrosine Kinase Inhibitorsmentioning

confidence: 76%

Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer

Kauffmann-Guerrero

Kahnert

Huber

2020

Drugs

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Non-small-cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases and is the leading cause of cancer-related deaths. Most NSCLC patients are diagnosed with advanced disease and require systemic treatment. Despite emerging advances in chemotherapy and immunotherapy, the prognosis of stage IV patients remains poor. However, the discovery of oncogenic driver mutations including mutations in the epidermal growth factor receptor (EGFR), the anaplastic lymphoma kinase (ALK) and others, characterize a subset of patients with the opportunity of targeted therapies. Fusions between the ALK and echinoderm microtubule-associated protein-like 4 (EML4) are present in ∼ 3–5% of patients with NSCLC. Several first-, second-, and third-generation ALK tyrosine kinase inhibitors (TKIs) have been developed in the last decade and have tremendously changed treatment options and outcomes of ALK-positive NSCLC patients. With increasing treatment options, treatment sequence decisions have become more and more complex. ALK-mutations, fusion variants, or activation of by-pass pathways result in treatment resistance during the course of treatment in nearly all patients. Mutation-guided treatment sequencing can lead to better outcomes, and re-biopsy or liquid-biopsy should be performed whenever possible in case of disease progression in ALK-rearranged patients. In the future, combinational treatment of ALK TKIs with other pathway-inhibitors might further improve patients’ treatment options and outcomes. Here, we review the data for currently available ALK TKIs, discuss approaches of treatment sequencing, and give an outlook on emerging developments.

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“…Peled et al. 29 reported that lorlatinib showed outstanding extracranial and intracranial efficacy in ALK/ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) (+) NSCLC. The CROWN trial investigators also found that those who received lorlatinib had significantly longer PFS than those who received crizotinib.…”

Section: Discussionmentioning

confidence: 99%

“…17,23 Furthermore, the third-generation ALK inhibitor lorlatinib was shown to be consistent in providing the best PFS and ORR in patients with ALK gene rearrangement NSCLC, through direct and indirect comparison of the evidence. Peled et al 29 reported that lorlatinib showed outstanding extracranial and intracranial efficacy in ALK/ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) (þ) NSCLC. The CROWN trial investigators also found that those who received lorlatinib had significantly longer PFS than those who received crizotinib.…”

Section: Discussionmentioning

confidence: 99%

First-line treatments for patients with advanced ALK gene rearrangements in NSCLC: a systematic review and network meta-analysis

et al. 2022

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Objective To conduct a network meta-analysis of randomised controlled trials to determine the optimal clinical choice of first-line therapy for patients with ALK receptor tyrosine kinase ( ALK) gene rearrangement non-small cell lung cancer (NSCLC). Methods Clinical trials in patients with histologically confirmed ALK gene rearrangement NSCLC, that included ALK inhibitors as first-line therapy, were identified using database searches. A Bayesian network meta-analysis was conducted to calculate the efficacy and safety of the included first-line treatments. Results Nine trials with 2,407 patients were included for analyses. Lorlatinib was better than brigatinib for progression-free survival (PFS) (hazard ratio 0.79, 95% confidence interval 0.63, 0.98). In subgroup analyses, lorlatinib exhibited the highest probability of best PFS ranking in patients with or without baseline brain metastases (38% and 80%, respectively); brigatinib had the highest probability of best PFS ranking among Asian patients (47%). Alectinib offered the highest survival advantage (57% probability), while lorlatinib was likely to be the best treatment for an objective response (41% probability). Alectinib displayed the highest probability of being ranked lowest for grade ≥3 adverse events (86%). Conclusions Lorlatinib was associated with the best PFS overall, and was suitable for patients with or without brain metastases. Brigatinib was associated with the best PFS in Asian patients.

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GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients

Cited by 24 publications

References 28 publications

Tumor‑associated macrophage‑derived exosomes promote EGFR‑TKI resistance in non‑small cell lung cancer by regulating the AKT, ERK1/2 and STAT3 signaling pathways

Tumor‑associated macrophage‑derived exosomes promote EGFR‑TKI resistance in non‑small cell lung cancer by regulating the AKT, ERK1/2 and STAT3 signaling pathways

Treatment Sequencing for Anaplastic Lymphoma Kinase-Rearranged Non-Small-Cell Lung Cancer

First-line treatments for patients with advanced ALK gene rearrangements in NSCLC: a systematic review and network meta-analysis

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