MEK114653: A randomized, multicenter, phase II study to assess efficacy and safety of trametinib (T) compared with docetaxel (D) in KRAS-mutant advanced non–small cell lung cancer (NSCLC).

• DOI: 10.1200/jco.2013.31.15_suppl.8029
• Publication Date: 2020-03-11T19:43:13Z
• Authors: George R. Blumens...; Egbert F. Smit; David Planchard; Dong-Wan Kim; Jacques Cadranel; Tommaso De Pas; Frank Dunphy; Katalin Udud; Myung-Ju Ahn; Nasser H. Hanna; Joo-Hang Kim; Julien Mazieres; Sang-We Kim; Paul Baas; Erica Rappold; Suman Redhu; Kevin M. Bellew; Michael R. W. Streit; Frank S. Wu; Pasi A. Janne
• Keywords: Clinical endpoint; Trametinib; Progression-free survival; Interim analysis

8029 Background: KRAS mutations are detected in 25% of NSCLC, and there no approved targeted therapies for this subset NSCLC. D, an second-line treatment has a response rate < 10%. T is reversible, highly selective allosteric inhibitor MEK1/2 activation kinase activity. This phase II trial (NCT01362296) evaluated the efficacy vs D pts with advanced KRAS-mutant NSCLC who had received prior platinum-based chemotherapy. Methods: Pts were randomized 2:1 to (2 mg QD) or (75 mg/m 2 IV every 3 weeks) stratified by type mutational status gender. Crossover other arm after progressive disease was allowed. Primary endpoint PFS (modified ITT; mITT). Secondary endpoints OS, ORR, duration response, safety. OS compared using log-rank test. The stopped early futility at planned interim analysis; 92 events reported time study termination. Results: Between September 2011 July 2012, 134 (89) (45); 129 Mean age 61.4 y 53% male. In mITT, 61/86 (71%) on 31/43 (72%) event. HR 1.14 (95% CI, 0.75-1.75; P = .5197) median 11.7 11.4 wk D. ORR 12% (10/86) (5/43). With 27 (31%) deaths 15 (35%) 0.97 0.52-1.83; P= .934). Five fatal SAEs during but none D; 1 unspecified death considered related T. Frequent AEs rash (59%), diarrhea (47%), nausea (34%), hypertension dyspnea (33%). Grade 3/4 (16%/0), (7%/3%), (6%/3%), (6%/0), asthenia (6%/0). Rate 15% Conclusions: did not improve KRAS-mutation–positive However, suggests that effort better identify responsive warranted. safety profile favor T, is, general, consistent overall profile. Clinical information: NCT01362296.