Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis

Ramalingam, Sendhilnathan; Gray, J.E.; Ohe, Yuichiro; Cho, B.C.; Vansteenkiste, J.; Zhou, C.; Reungwetwattana, Thanyanan; Cheng, Ying; Chewaskulyong, B.; Shah, Riyaz; Lee, K.H.; Cheema, Puneet S.; Tiseo, Marcello; John, Thomas; Lin, Meng-Chih; Imamura, Fumio; Hodge, Rachel; Rukazenkov, Yuri; Soria, Jean Charles; Planchard, David

doi:10.1093/annonc/mdz394.076

Cited by 47 publications

(30 citation statements)

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“…Given the success of the FLAURA study, there is an increasing number of patients receiving osimertinib as first-line treatment when diagnosed with EGFR-mutated NSCLC. 22 So far, there are no prospective data on patients who develop LM while on first-line osimertinib or whether they continue to have clinical benefit with continuation of osimertinib treatment along with other local therapy. These issues warrant further exploration and need to be addressed in future studies.…”

Section: Discussionmentioning

confidence: 99%

Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status

Lee

Choi

Han

et al. 2020

Journal of Thoracic Oncology

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Introduction: Osimertinib, a third-generation EGFR tyrosine kinase inhibitor, efficiently penetrates the blood-brain barrier. This study explored whether treatment with osimertinib leads to improved overall survival (OS) for patients with EGFR-mutated NSCLC with leptomeningeal metastases (LM) compared with those not treated with osimertinib. Methods: From October 2008 to October 2019, patients with EGFR-mutated NSCLC and cytologically confirmed LM were retrospectively analyzed for OS according to osimertinib treatment and T790M mutational status. The OS was defined as the time from the diagnosis of LM to death. Results: For the 351 patients with LM included in the analysis, the median OS (mOS) was 8.1 months (95% confidence interval [CI]: 7.2-9.0). T790M mutation was detected in 88 of 197 patients tested, and a total of 110 patients were treated with osimertinib after LM. No difference in mOS according to T790M mutational status (10.1 mo [95% CI: 4.31-15.82] versus 9.0 [95% CI: 6.81-11.21], p ¼ 0.936) was found. Nevertheless, patients treated with osimertinib had a superior OS of 17.0 months (95% CI: 15.13-18.94) compared with those not treated with osimertinib who had a mOS of 5.5 months (95% CI: 4.34-6.63), regardless of T790M mutational status (hazard ratio: 0.36 [95% CI: 0.28-0.47], p < 0.001). This was also considerably longer even than the mOS of 8.7 months (95% CI: 7.01-10.39) of those who were never treated with osimertinib but had firstor second-generation EGFR tyrosine kinase inhibitors. Conclusions: Osimertinib is a promising treatment option for EGFR-mutated NSCLC with LM regardless of T790M mutational status.

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Section: Discussionmentioning

confidence: 99%

Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status

Lee

Choi

Han

et al. 2020

Journal of Thoracic Oncology

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“…Osimertinib, (OSI, AZD9291) is a third-generation, irreversible TKI of the epidermal growth factor receptor (EGFR-TKI) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations [ 13 ]. OSI initially gained FDA approval for patients with metastatic EGFR T790M-mutant NSCLC that had progressed on first- or second-generation EGFR TKIs and has subsequently achieved approval as a first-line treatment of EGFR-mutant lung cancer [ 6 , 13 , 14 ]. OSI is administered orally in the form of film-coated tablets (TAGRISSO ® ) containing OSI as mesylate.…”

Section: Introductionmentioning

confidence: 99%

Development of Liposomal Vesicles for Osimertinib Delivery to EGFR Mutation—Positive Lung Cancer Cells

Skupin-Mrugalska

Minko

2020

Pharmaceutics

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Osimertinib (OSI, AZD9291), is a third-generation, irreversible tyrosine kinase inhibitor (TKI) of the epidermal growth factor receptor (EGFR) that selectively inhibits both EGFR-TKI–sensitizing and EGFR T790M resistance mutations. OSI has been approved as a first-line treatment of EGFR-mutant lung cancer and for metastatic EGFR T790M-mutant non-small cell lung cancer. Liposome-based delivery of OSI can provide a new formulation of the drug that can be administered via alternative delivery routes (intravenous, inhalation). In this manuscript, we report for the first time development and characterization of liposomal OSI formulations with diameters of ca. 115 nm. Vesicles were composed of phosphatidylcholines with various saturation and carbon chain lengths, cholesterol and pegylated phosphoethanolamine. Liposomes were loaded with OSI passively, resulting in a drug being dissolved in the phospholipid matrix or actively via remote-loading leading to the formation of OSI precipitate in the liposomal core. Remotely loaded liposomes were characterized by nearly 100% entrapment efficacy and represent a depot of OSI. Passively-loaded vesicles released OSI following the Peppas-Sahlin model, in a mechanism combining drug diffusion and liposome relaxation. OSI-loaded liposomes composed of l-α-phosphatidylcholine (egg-PC) demonstrated a higher toxicity in non-small lung cancer cells with EGFR T790M resistance mutation (H-1975) when compared with free OSI. Developed OSI formulations did not show antiproliferative activity in vitro in healthy lung epithelial cells (MRC-5) without the EGFR mutation.

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“…Following the successful experience in advanced/metastatic setting with multiple EGFR TKIs approved in molecularly selected patients [ 15 , 16 , 17 , 18 , 19 ] different studies have sought to demonstrate a survival advantage with the use of these agents as adjuvant therapy in EGFR-mutated radically resected NSCLCs ( Table 1 ). Nevertheless the role of co-mutations remains unclear [ 20 ].…”

Section: Epidermal Growth Factor Receptor (Egfr) Mutationsmentioning

confidence: 99%

Targeted Therapies in Early Stage NSCLC: Hype or Hope?

Friedlaender

Addeo

Russo

et al. 2020

IJMS

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Non-small-cell lung cancer (NSCLC) represents roughly 85% of lung cancers, with an incidence that increases yearly across the world. The introduction in clinical practice of several new and more effective molecules has led to a consistent improvement in survival and quality of life in locally advanced and metastatic NSCLC. In particular, oncogenic drivers have indeed transformed the therapeutic algorithm for NSCLC. Nearly 25% of patients are diagnosed in an early stage when NSCLC is still amenable to radical surgery. In spite of this, five-year survival rates for fully resected early stage remains rather disappointing. Adjuvant chemotherapy has shown a modest survival benefit depending on the stage, but more than half of patients relapse. Given this need for improvement, over the last years different targeted therapies have been evaluated in early-stage NSCLC with no survival benefit in unselected patients. However, the identification of reliable predictive biomarkers to these agents in the metastatic setting, the design of molecularly-oriented studies, and the availability of novel potent and less toxic agents opened the way for a novel era in early stage NSCLC treatment. In this review, we will discuss the current landscape of targeted therapeutic options in early NSCLC.

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Osimertinib vs comparator EGFR-TKI as first-line treatment for EGFRm advanced NSCLC (FLAURA): Final overall survival analysis

Cited by 47 publications

References 0 publications

Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status

Osimertinib Improves Overall Survival in Patients With EGFR-Mutated NSCLC With Leptomeningeal Metastases Regardless of T790M Mutational Status

Development of Liposomal Vesicles for Osimertinib Delivery to EGFR Mutation—Positive Lung Cancer Cells

Targeted Therapies in Early Stage NSCLC: Hype or Hope?

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