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Multicenter Phase II Trial of YM155, a Small-Molecule Suppressor of Survivin, in Patients With Advanced, Refractory, Non–Small-Cell Lung Cancer

2009; Lippincott Williams & Wilkins; Volume: 27; Issue: 27 Linguagem: Inglês

10.1200/jco.2008.21.1862

1527-7755

Giuseppe Giaccone, Petr Zatloukal, Jaromı́r Roubec, Karijn Floor, J Musil, M Kůta, Rob J. van Klaveren, Subhash Chaudhary, Adrie Gunther, Setareh Shamsili,

Lung Cancer Research Studies

Purpose To evaluate the antitumor activity and safety of YM155, a novel, small-molecule suppressor of survivin, as single-agent therapy in patients with previously treated, advanced non–small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIb/IV NSCLC who had experienced treatment failure during one or two prior chemotherapy regimens (at least one of which was platinum based) received YM155 as a continuous intravenous infusion (4.8 mg/m 2 /d) over 168 hours followed by observation for 14 days in 21-day treatment cycles. The primary end point was objective tumor response rate (ORR). Secondary end points included duration of stable disease (SD), progression-free survival (PFS), overall survival (OS), safety and pharmacokinetic profiles, and pharmacodynamic evaluations. Results Thirty-seven patients received YM155. Two patients achieved a confirmed partial response, with an ORR of 5.4% (95% CI, 0.7% to 18.2%). An additional 14 patients (37.8%) achieved SD resulting in a disease control rate of 43.2% (95% CI, 27.1% to 60.5%). Median duration of PFS was 1.7 months (95% CI, 1.3 to 2.8 months). Median duration of OS was 6.6 months (95% CI, 4 to 12.2 months), with a 1-year survival rate of 35.1%. Treatment with YM155 was well tolerated with the majority of treatment discontinuations not treatment related. Conclusion YM155 exhibited modest single-agent activity in patients with refractory, advanced NSCLC. A favorable safety/tolerability profile was reported. Further evaluation of YM155 in combination with chemotherapy and other targeted agents may be warranted.