Results from ARQ 197-209: A global randomized placebo-controlled phase II clinical trial of erlotinib plus ARQ 197 versus erlotinib plus placebo in previously treated EGFR inhibitor-naive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)

Author/Creator:	Rodryg Ramlau, Wolfram Brugger, Wallace Akerley, Edward Graeme Garmey, Dora Ferrari, Sergey Orlov, J. von Pawel, Lecia V. Sequist, David E. Gerber, Joan H. Schiller
Publication Year:	2010
Subject:	Oncology Cancer Research medicine.medical_specialty business.industry non-small cell lung cancer (NSCLC) Pharmacology medicine.disease Placebo Clinical trial Therapy naive Internal medicine medicine Clinical endpoint Erlotinib business Previously treated EGFR inhibitors medicine.drug
Source:	Journal of Clinical Oncology. 28:LBA7502-LBA7502
ISSN:	1527-7755 0732-183X
Description:	LBA7502 Background: Orally administered ARQ197 is a selective, non-ATP competitive inhibitor of c-MET (MET), a receptor TK implicated in cancer cell migration, invasion, and proliferation. Dual EGFR-MET inhibition is a promising strategy for overcoming MET-mediated resistance to EGFR inhibitors. A prior phase I trial demonstrated the safety of ARQ197 plus erlotinib and suggested activity in patients (pts) with advanced NSCLC. Methods: This is a global, randomized, placebo-controlled, double-blind trial comparing erlotinib plus ARQ197 (E+A) versus erlotinib plus placebo (E+P). Archival tissue was collected for all pts for k-RAS, EGFR, and MET analyses. The primary endpoint was PFS; secondary endpoints included safety, ORR, OS, and subgroup analyses. Results: 167 pts were randomized to E+A (84 pts) or E+P (83 pts). Mean age was 63 yrs and baseline characteristics were well balanced for sex (39%/41% F); race (93%/96% white) and smoking history (20%/22% never smoker). Imbalances were seen among treatment arms in NSCLC histology (54%/64% adeno) and predictive molecular genotypes: EGFR mutations (7%/13%) and k-RAS mutations (12%/6%). Final PFS was prolonged with E+A (median = 16.1 wks) vs E+P (9.7 wks) among ITT pts (HR 0.81 [95% CI 0.57, 1.15]; p=0.23). Planned multivariable Cox regression model adjusting for prognostic factors (including histology, genotype) yielded PFS HR 0.68 (95% CI 0.47, 0.98; p Conclusions: Combined with erlotinib in the treatment of second/third-line EGFR-inhibitor naïve NSCLC, ARQ-197 is well-tolerated and prolongs PFS. Particular benefit is observed among pts with non-squamous histology, k-RAS mutations, and EGFR wild-type status. [Table: see text]
Database:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::6e6967ac9b8376301cd0396dc82b02e7 https://doi.org/10.1200/jco.2010.28.18_suppl.lba7502 View in EDS