BACKGROUND: The src family of kinases may play a role in the malignant phenotype through effects on migration, motility, adhesion and proliferation. The activity of saracatinib, an orally available inhibitor of src kinases, was evaluated in patients with advanced, platinum-pretreated NSCLC. PATIENTS AND METHODS: Eligible patients with advanced NSCLC of any histologic subtype and who had obtained a best response to prior platinum-based chemotherapy of at least stable disease received saracatanib 175 mg orally daily in a 28 day cycle. The primary end point was the proportion of patients progression-free after 4 cycles (16 weeks) of therapy; 8 such patients of 32 evaluable were required to deem the therapy active. Immunohistochemistry for src expression was performed on archival tissue from enrolled patients. RESULTS: Thirty-seven patients received a median of 2 cycles (range, 1-14) each. Six of 31 evaluable patients were progression-free at 16 weeks. Two partial responses were observed, lasting 3.7 and 14.6 months; 1 responder had an EGFR exon 19 deletion. An additional 4 patients had stable disease for at least 4 cycles. The median progression-free and overall survival times were 1.8 and 7.6 months. No correlation between src protein expression and outcome was observed. CONCLUSIONS: There may be a subset of saracatinib-responsive NSCLC that is currently molecularly undefined. Further studies of this agent in a population preselected for target mutations that potentially relevant to src pathways, such as EGFR, should be considered.
BACKGROUND: The src family of kinases may play a role in the malignant phenotype through effects on migration, motility, adhesion and proliferation. The activity of saracatinib, an orally available inhibitor of src kinases, was evaluated in patients with advanced, platinum-pretreated NSCLC. PATIENTS AND METHODS: Eligible patients with advanced NSCLC of any histologic subtype and who had obtained a best response to prior platinum-based chemotherapy of at least stable disease received saracatanib 175 mg orally daily in a 28 day cycle. The primary end point was the proportion of patients progression-free after 4 cycles (16 weeks) of therapy; 8 such patients of 32 evaluable were required to deem the therapy active. Immunohistochemistry for src expression was performed on archival tissue from enrolled patients. RESULTS: Thirty-seven patients received a median of 2 cycles (range, 1-14) each. Six of 31 evaluable patients were progression-free at 16 weeks. Two partial responses were observed, lasting 3.7 and 14.6 months; 1 responder had an EGFR exon 19 deletion. An additional 4 patients had stable disease for at least 4 cycles. The median progression-free and overall survival times were 1.8 and 7.6 months. No correlation between src protein expression and outcome was observed. CONCLUSIONS: There may be a subset of saracatinib-responsive NSCLC that is currently molecularly undefined. Further studies of this agent in a population preselected for target mutations that potentially relevant to src pathways, such as EGFR, should be considered.
Authors: S M Reddy; S Kopetz; J Morris; N Parikh; W Qiao; M J Overman; D Fogelman; I Shureiqi; C Jacobs; Z Malik; C A Jimenez; R A Wolff; J L Abbruzzese; G Gallick; C Eng Journal: Invest New Drugs Date: 2015-06-12 Impact factor: 3.850
Authors: Melanie Spitzner; Reinhard Ebner; Hendrik A Wolff; B Michael Ghadimi; Jürgen Wienands; Marian Grade Journal: Cancers (Basel) Date: 2014-09-29 Impact factor: 6.639
Authors: Kian Ngiap Chua; Li Ren Kong; Wen Jing Sim; Hsien Chun Ng; Weijie Richard Ong; Jean Paul Thiery; Hung Huynh; Boon Cher Goh Journal: Oncotarget Date: 2015-10-06
Authors: Luigi Formisano; Valentina D'Amato; Alberto Servetto; Simona Brillante; Lucia Raimondo; Concetta Di Mauro; Roberta Marciano; Roberta Clara Orsini; Sandro Cosconati; Antonio Randazzo; Sarah J Parsons; Nunzia Montuori; Bianca Maria Veneziani; Sabino De Placido; Roberta Rosa; Roberto Bianco Journal: Oncotarget Date: 2015-09-22