Symptom and Quality of Life Benefit of Afatinib in Advanced Non–Small-Cell Lung Cancer Patients Previously Treated with Erlotinib or Gefitinib: Results of a Randomized Phase IIb/III Trial (LUX-Lung 1)

Hirsh, Vera; Cadranel, Jacques; Cong, Xiuyu Julie; Fairclough, Diane L.; Finnern, Henrik W.; Lorence, Robert M.; Miller, V. A.; Palmer, Michael; Yang, James Chih‐Hsin

doi:10.1097/jto.0b013e3182773fce

Cited by 69 publications

(58 citation statements)

References 21 publications

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“…250 Erlotinib, gefitinib, or afatinib may be continued in patients with sensitizing EGFR mutations whose disease has progressed after first-line therapy. 15,[218][219][220] Osimertinib is recommended for patients with T790M whose disease becomes resistant to erlotinib, afatinib, or gefitinib. 39 Afatinib/cetuximab may be considered for patients with sensitizing EGFR mutations whose disease has progressed after EGFR TKI therapy and chemotherapy.…”

Section: Second-line and Beyond (Subsequent) Systemic Therapymentioning

confidence: 99%

“…[214][215][216][217] The NCCN panel recommends continuing erlotinib, gefitinib, or afatinib and considering local therapy in patients with asymptomatic progression; however, treatment varies for patients with symptomatic progression (see NSCL-19, page 508). [218][219][220] For the 2017 updates (Versions 1 and 4), the NCCN panel revised the recommendations for patients with sensitizing EGFR mutations whose disease has progressed on erlotinib, gefitinib, or afatinib. Osimertinib is now recommended (category 1) for patients with symptomatic brain metastases.…”

Section: Continuation Of Erlotinib Gefitinib or Afatinib After Progmentioning

confidence: 99%

See 1 more Smart Citation

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Ettinger¹,

Wood²,

Aisner³

et al. 2017

J Natl Compr Canc Netw

1,106

1,005

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Section: Second-line and Beyond (Subsequent) Systemic Therapymentioning

confidence: 99%

Section: Continuation Of Erlotinib Gefitinib or Afatinib After Progmentioning

confidence: 99%

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Ettinger¹,

Wood²,

Aisner³

et al. 2017

J Natl Compr Canc Netw

1,106

1,005

View full text Add to dashboard Cite

show abstract

“…Finally, results of the LUX-Lung 1 study showed significantly improved global qol, physical function, and fatigue with afatinib use. In addition, afatinib also improved lung cancer-related symptoms such as cough, dyspnea, and pain, and significantly delayed time to deterioration 50 .…”

Section: Benefits Of Egfr-tkismentioning

confidence: 99%

“…A phase iib/iii study (LUX-Lung 1) in patients failing chemotherapy and erlotinib or gefitinib found a tripling in median pfs to 3.3 months from 1.1 month (hr: 0.38; p < 0.0001) with the addition of afatinib (50 mg) to best supportive care 50 (Table iii). In addition, a subgroup analysis examined the benefit of afatinib in patients with the highest likelihood of EGFR mutations-that is, those with a complete or partial response on prior erlotinib or gefitinib, or with 48 weeks or more on treatment with erlotinib or gefitinib, or both 51 .…”

Section: Pretreated Patientsmentioning

confidence: 99%

A Personalized Approach to Treatment: Use of egfr Tyrosine Kinase Inhibitors for the Treatment of Non-Small-Cell Lung Cancer in Canada

et al. 2012

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Lung cancer is one of the most commonly diagnosed malignancies and the leading cause of cancer-related mortality in Canada. The heterogeneity of nsclc and the importance of linking new targeted agents to the appropriate disease subtype require an individualized approach to treatment. In patients with EGFR (epidermal growth factor receptor gene) mutations, egfr tyrosine kinase inhibitors (tkis) provide a highly effective treatment option, with improved toxicity compared with standard chemotherapy. However, the identification of mutation-positive patients is limited by a lack of funding for testing. The length of time required to receive test results and insufficient tissue from biopsies are additional limitations. In Canada, the use of egfr-tkis varies based on differences in provincial funding for both testing and treatment. With improvements in testing and access to funding for treatment, targeted use of egfr-tkis may greatly improve outcomes in nsclc.

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“…Indeed 79% and 68% of patients in the placebo and afatinib arms, respectively, received additional treatment. Afatinib treatment in LUX-Lung 1 was also associated with significant improvement in NSCLCrelated symptoms and quality of life (QoL; P 6 0.05) [72]. In the first-line setting, the clinical activity of afatinib was assessed in the proof-of-concept, Phase II LUX-Lung 2 study, which enrolled 129 patients with EGFR-mutation-positive NSCLC (>80% with Del19 or L858R mutations) [ [74].…”

Section: Pelitinib Av-412/mp-412 and Bms-599626mentioning

confidence: 99%

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

Rolfo

Giovannetti

Hong

et al. 2014

Cancer Treatment Reviews

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a b s t r a c tIntroduction: Treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) yields tumour responses in non-small cell lung cancer (NSCLC) patients harbouring activating EGFR mutations. However, even in long-lasting responses, resistance to EGFR TKIs invariably occurs. Areas covered: This review examines resistance mechanisms to EGFR TKI treatment, which mainly arise from secondary EGFR mutations. Other resistance-inducing processes include mesenchymal-epithelial transition factor (MET) amplification, epithelial-mesenchymal transformation, phenotypic change from NSCLC to small-cell lung carcinoma, and modifications in parallel signalling pathways. Current therapeutic strategies to overcome these EGFR TKI resistance mechanisms focus on the inhibition or blocking of multiple members of the ErbB family. Several molecules which target multiple ErbB receptors are being investigated in NSCLC and other indications including afatinib, an ErbB Family Blocker, as well as dacomitinib and lapatinib. Novel, non-quinazoline, EGFR inhibitors, that also target EGFR activating and resistance (T790M) mutations, are currently under clinical development. Other therapeutic strategies include inhibition of parallel and downstream pathways, using agents which target heat shock protein (HSP)90 or http://dx.doi.org/10.1016/j.ctrv.2014.05.009 0305-7372/Ó 2014 Elsevier Ltd. All rights reserved.Abbreviations: AEG-1, astrocyte elevated gene-1; ALK, anaplastic lymphoma kinase; ATP, adenosine triphosphate; BARD1, BRCA1-associated protein 1; BIM, B-cell lymphoma 2 interacting mediator of cell death; BRAF, v-raf murine sarcoma viral oncogene homolog B1; BRCA1, breast cancer 1, early onset; CNS, central nervous system; CRKL, crk-like protein; DCR, disease control rate; EGFR, epidermal growth factor receptor; EMT, epithelial-mesenchymal transformation; EphB4, ephrin type-B receptor 4; ER, oestrogen receptor; ERK, extracellular-signal-regulated kinases; HER, human epidermal growth factor receptor; HGF, hepatocyte growth factor; HSP90, heat shock protein 90; IGF-1R, insulin-like growth factor 1 receptor; KRAS, Kirsten rat sarcoma viral oncogene homologue; MBP-QP, mutation-biased PCR quenching probe; MEK, mitogen-activated protein kinase; MET, mesenchymal-epithelial transition factor; mRNA, messenger RNA; mTOR, mammalian target of rapamycin; NF-jB, nuclear factor kappa-light-chainenhancer of activated B cells; NSCLC, non-small-cell lung cancer; ORR, overall response rate; OS, overall survival; PARP, poly (ADP-ribose) polymerase; PCR, polymerase chain reaction; PFS, progression free survival; PI3K, phosphoinositide-3-kinase; PIK3CA, phosphoinositide-3-kinase, catalytic, alpha polypeptide; PTEN, phosphatase and tensin homologue; RECIST, Response Evaluation Criteria in Solid Tumours; RR, response rate; SCLC, small-cell lung cancer; TGF, transforming growth factor; TKI, tyrosine kinase inhibitors; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor. E-mail address: christian.rolfo@uza.be (C. Rolfo).Can...

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Symptom and Quality of Life Benefit of Afatinib in Advanced Non–Small-Cell Lung Cancer Patients Previously Treated with Erlotinib or Gefitinib: Results of a Randomized Phase IIb/III Trial (LUX-Lung 1)

Abstract: In the LUX-Lung 1 trial, the addition of afatinib to BSC significantly improved non-small-cell lung cancer-related symptoms (cough, dyspnea, and pain), fatigue, physical functioning, and HRQoL and significantly delayed time to deterioration of cough.

Cited by 69 publications

References 21 publications

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

Non–Small Cell Lung Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology

A Personalized Approach to Treatment: Use of egfr Tyrosine Kinase Inhibitors for the Treatment of Non-Small-Cell Lung Cancer in Canada

Novel therapeutic strategies for patients with NSCLC that do not respond to treatment with EGFR inhibitors

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