BACKGROUND: Mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) predict longer overall survival (OS) and response to EGFR tyrosine kinase inhibitors (TKIs). The clinical relevance of different mutations in terms of response to TKIs and prognosis is still unclear. OBJECTIVES: The aims of the present study were to assess the relationship between mutations in exon 18, 19 and 21 in patients treated with TKIs and their clinical outcomes, and evaluate the role of specific point mutations. METHODS: We included in this analysis 55 patients with metastatic NSCLC and mutations in exon 18, 19 and 21, treated in our center between 2004 and 2014. All patients received treatment with TKIs in first and/or subsequent lines. Endpoints analyzed were OS (primary) and time to progression (TTP) (secondary), according to exon mutations and specific point mutations. RESULTS: A strong negative prognostic association for OS (p = 0.02) and TTP (p = 0.03) was found for exon 18 mutations compared with exon 19 deletions . A trend toward a longer median OS was observed in exon 19 deletions versus exon 21 point mutations (+6.6 months), although more exon 19-mutated patients had brain metastases at diagnosis. Comparing each mutation, p.E746_A750del and p.E746_T751del of exon 19 and p.L858R mutation of exon 21, a trend toward improved OS in p.E746_A750del was found. CONCLUSION: In this analysis, exon 19 deletions were associated with better outcomes, despite a higher percentage of brain metastases in this group. The prognostic relevance of p.E746_A750del requires further studies.
BACKGROUND: Mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) predict longer overall survival (OS) and response to EGFR tyrosine kinase inhibitors (TKIs). The clinical relevance of different mutations in terms of response to TKIs and prognosis is still unclear. OBJECTIVES: The aims of the present study were to assess the relationship between mutations in exon 18, 19 and 21 in patients treated with TKIs and their clinical outcomes, and evaluate the role of specific point mutations. METHODS: We included in this analysis 55 patients with metastatic NSCLC and mutations in exon 18, 19 and 21, treated in our center between 2004 and 2014. All patients received treatment with TKIs in first and/or subsequent lines. Endpoints analyzed were OS (primary) and time to progression (TTP) (secondary), according to exon mutations and specific point mutations. RESULTS: A strong negative prognostic association for OS (p = 0.02) and TTP (p = 0.03) was found for exon 18 mutations compared with exon 19 deletions . A trend toward a longer median OS was observed in exon 19 deletions versus exon 21 point mutations (+6.6 months), although more exon 19-mutated patients had brain metastases at diagnosis. Comparing each mutation, p.E746_A750del and p.E746_T751del of exon 19 and p.L858R mutation of exon 21, a trend toward improved OS in p.E746_A750del was found. CONCLUSION: In this analysis, exon 19 deletions were associated with better outcomes, despite a higher percentage of brain metastases in this group. The prognostic relevance of p.E746_A750del requires further studies.
Authors: David M Jackman; Beow Y Yeap; Lecia V Sequist; Neal Lindeman; Alison J Holmes; Victoria A Joshi; Daphne W Bell; Mark S Huberman; Balazs Halmos; Michael S Rabin; Daniel A Haber; Thomas J Lynch; Matthew Meyerson; Bruce E Johnson; Pasi A Jänne Journal: Clin Cancer Res Date: 2006-07-01 Impact factor: 12.531
Authors: Hiroyuki Yasuda; Eunyoung Park; Cai-Hong Yun; Natasha J Sng; Antonio R Lucena-Araujo; Wee-Lee Yeo; Mark S Huberman; David W Cohen; Sohei Nakayama; Kota Ishioka; Norihiro Yamaguchi; Megan Hanna; Geoffrey R Oxnard; Christopher S Lathan; Teresa Moran; Lecia V Sequist; Jamie E Chaft; Gregory J Riely; Maria E Arcila; Ross A Soo; Matthew Meyerson; Michael J Eck; Susumu S Kobayashi; Daniel B Costa Journal: Sci Transl Med Date: 2013-12-18 Impact factor: 17.956
Authors: Gregory J Riely; William Pao; Duykhanh Pham; Allan R Li; Naiyer Rizvi; Ennapadam S Venkatraman; Maureen F Zakowski; Mark G Kris; Marc Ladanyi; Vincent A Miller Journal: Clin Cancer Res Date: 2006-02-01 Impact factor: 12.531
Authors: Vincent A Miller; Mark G Kris; Neelam Shah; Jyoti Patel; Christopher Azzoli; Jorge Gomez; Lee M Krug; William Pao; Naiyer Rizvi; Barbara Pizzo; Leslie Tyson; Ennapadam Venkatraman; Leah Ben-Porat; Natalie Memoli; Maureen Zakowski; Valerie Rusch; Robert T Heelan Journal: J Clin Oncol Date: 2004-03-15 Impact factor: 44.544
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: Sharon Barr; Stuart Thomson; Elizabeth Buck; Suzanne Russo; Filippo Petti; Izabela Sujka-Kwok; Alexandra Eyzaguirre; Maryland Rosenfeld-Franklin; Neil W Gibson; Mark Miglarese; David Epstein; Kenneth K Iwata; John D Haley Journal: Clin Exp Metastasis Date: 2008-01-31 Impact factor: 5.150
Authors: J L Kuiper; S M S Hashemi; E Thunnissen; P J F Snijders; K Grünberg; E Bloemena; D Sie; P E Postmus; D A M Heideman; E F Smit Journal: Br J Cancer Date: 2016-11-22 Impact factor: 7.640
Authors: Samer Al-Saad; Elin Richardsen; Thomas K Kilvaer; Tom Donnem; Sigve Andersen; Mehrdad Khanehkenari; Roy M Bremnes; Lill-Tove Busund Journal: PLoS One Date: 2017-07-25 Impact factor: 3.240