Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial

Yang, James Chih Hsin; Shih, Jin‐Yuan; Su, Wu Chou; Hsia, Te Chun; Tsai, Chun Ming; Ou, Sai Hong Ignatius; Yu, Chong‐Jen; Chang, Gee Chen; Ho, Ching Liang; Sequist, Lecia V.; Dudek, Arkadiusz Z.; Shahidi, Mehdi; Cong, Xiuyu Julie; Lorence, Robert M.; Yang, Pan Chyr; Miller, Vincent A.

doi:10.1016/s1470-2045(12)70086-4

Cited by 370 publications

(257 citation statements)

References 29 publications

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“…Results of the EURTAC study (2) have led to the approval of Erlotinib (TARCEVA Genentech, Inc., South San Francisco, CA, and OSI Pharmaceuticals, Inc., Melville, NY, USA), already approved for the treatment of locally advanced or metastatic NSCLC following the failure of at least one prior chemotherapy regimen, for the first-line treatment of same stage patients carrying an EGFR mutation. Results of the phase II LUX-LUNG 2 study have demonstrated that afatinib, an irreversible ErbB family blocker of EGFR, HER2 and HER4, showed significant activity in EGFR mutated patients (36). Moreover, preliminary results from the randomised phase III study LUX-LUNG 3 have demonstrated that afatinib significantly prolonged PFS compared to pemetrexed/cisplatinum treatment (37).…”

Section: Clinically-relevant Target Drugsmentioning

confidence: 99%

Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation

Ulivi

Zoli

Capelli

et al. 2013

Molecular and Clinical Oncology

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Abstract. In recent years, a number of new agents that target specific molecular pathways in non-small cell lung cancer (NSCLC) have been investigated. Much effort has been focused on identifying specific markers that are predictive of treatment response, given that a tailored approach would maximise the therapeutic index and cost-effectiveness. Gefitinib and erlotinib are selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) and have produced good results in selected cases in terms of objective response rate and overall survival. At present, EGFR gene mutations are considered the most important predictors of clinical response to TKI therapy and tumour characterisation for these alterations is mandatory prior to any decision making. Echinoderm microtubule-like protein 4-anaplastic lymphoma kinase (EML4-ALK) translocation is another alteration capable of predicting the efficacy of anti-ALK agents, such as crizotinib. Moreover, emerging target agents, such as MET inhibitors, are likely to increase the amount of molecular characterisation required before a decision is made on treatment. The main limiting factor for adequate characterisation of metastatic NSCLC patients is the small quantity of tumour cells available for molecular analysis. In this study, we provided an overview of the most important and clinically relevant target agents in NSCLC patients as well as the most important mechanisms of resistance. The issue of the scant amount of biological samples available for analysis as well as alternative sampling approaches such as plasma-or serum-derived DNA were also examined.

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Section: Clinically-relevant Target Drugsmentioning

confidence: 99%

Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation

Ulivi

Zoli

Capelli

et al. 2013

Molecular and Clinical Oncology

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“…Despite the initial success of these drugs in all patients, the median progression free survival was 12-16 months (4,7,11). Acquired resistance to EGFR-TKIs has been attributed to several molecular mechanisms, although the resistance of patients with unknown etiology is ~35% (12).…”

Section: Introductionmentioning

confidence: 99%

The level of serum carcinoembryonic antigen is a surrogate marker for the efficacy of EGFR-TKIs but is not an indication of acquired resistance to EGFR-TKIs in NSCLC patients with EGFR mutationsm

Han

Cao

et al. 2017

Biomedical Reports

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Abstract. The aim of the present study was to define the relationship between carcinoembryonic antigen (CEA) and survival in non-small cell lung cancer (NSCLC) patients receiving epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and to investigate whether the level of serum CEA is related to the mechanism for acquisition of resistance to EGFR-TKIs. A total of 100 patients with advanced NSCLC (stage IIIB or stage IV) and harboring EGFR mutations were included. All patients received erlotinib or gefitinib treatment. The correlation between CEA serum level and clinical benefit from erlotinib or gefitinib treatment was analyzed. Patients were appraised by a review of data from a prospective re-biopsy protocol for lung cancer patients with an EGFR-mutated phenotype with acquired resistance to EGFR-TKI therapy. Of 100 patients, 49 and 21 patients carried high and low level of CEA, respectively; 30 carried normal CEA. Median progression-free survival was 6.4 and 4.5 months in patients with high and low level of CEA, respectively (P= 0.027). Median PFS of patients in low-CEA group longer than that of those with normal level of tumors (3.0 months; P= 0.002). The difference between groups L and N was not significant regarding objective response rate and overall survival. No significant difference was found in three groups of acquired resistance to EGFR-TKIs. The relative CEA level could predict benefit of EGFR-TKI therapy in advanced NSCLC, but could not predict acquired resistance to EGFR-TKIs.

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“…19 Complete response to afatinib has been reported in lung cancer with EGFR mutations (deletion 19 or L858R). 21 In comparison to first line doublet chemotherapy, afatinib improved progression-free survival in patients with EGFR-activating mutations, leading to its recent FDA approval. Afatinib is also a potent ERBB2 kinase inhibitor.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of a patient with Li–Fraumeni syndrome and metastatic lung adenocarcinoma harboring synchronous EGFR L858R and ERBB2 extracellular domain S310F mutations with the pan-HER inhibitor afatinib

Jia

Ali²,

Saad

et al. 2014

Cancer Biology & Therapy

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Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial

Cited by 370 publications

References 29 publications

Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation

Target therapy in NSCLC patients: Relevant clinical agents and tumour molecular characterisation

The level of serum carcinoembryonic antigen is a surrogate marker for the efficacy of EGFR-TKIs but is not an indication of acquired resistance to EGFR-TKIs in NSCLC patients with EGFR mutationsm

Successful treatment of a patient with Li–Fraumeni syndrome and metastatic lung adenocarcinoma harboring synchronous EGFR L858R and ERBB2 extracellular domain S310F mutations with the pan-HER inhibitor afatinib

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