Amrubicin (AMR) and cardiotoxicity in second-line treatment of small cell lung cancer (SCLC): A pooled analysis of left ventricular ejection fraction (LVEF) in two phase II trials

Abstract

e19019 Background: Amrubicin (AMR) is a third-generation synthetic anthracycline and a potent topoisomerase II inhibitor approved in Japan for the treatment of lung cancer. In Japanese pre and postmarking studies, AMR treatment was not associated with cardiotoxicity. The purpose of this analysis was to determine if AMR treatment of Western patients (pts) is associated with anthracycline-induced cardiomyopathy. Methods: To evaluate risk of cardiomyopathy, LVEF was measured by echocardiogram or by multiple gated acquisition (MUGA) scan and pooled from pts enrolled in 2 trials of IV AMR, 40 mg/m2/day x 3 days q 21 days for second-line treatment of sensitive or refractory SCLC. Pts with measurable disease, ECOG PS 0–2, LVEF ≥50%, and prior platinum-based treatment were assessed at baseline (BL), cycles 3, 6, then every 2 cycles, and end of treatment. Pts were to be assessed by the same method (ECHO or MUGA) throughout the study. Pts with a persistent ≥20% decrease in LVEF during treatment were to be removed from the study. Results: 112 patients were treated (sensitive n=43, median 6 cycles; refractory, n=69, median 5 cycles) and had at least 1 LVEF assessment. Median age was 63 years and median BL LVEF was 60%. Changes in LVEF from baseline were minimal ( Table ) and similar across cumulative dosing groups including 15 pts who received a cumulative dose of >1,000 mg/m2 AMR. Two refractory pts (1.8%) experienced drops in LVEF >20%. One had BL LVEF of 85%, then 60% at cycle 3, and 70% subsequently with ongoing therapy. The second, with a history of cardiomegaly, had LVEF of 55% at BL, cycle 3, and 5 by ECHO, and 29% at the time of progression after cycle 9 (cumulative AMR dose 840 mg/m2) by MUGA. The patient died due to progressive disease with no evidence of CHF. Conclusions: In this pooled analysis of SCLC pts, LVEF remained stable even in pts with cumulative AMR dosing >1,000 mg/m2. AMR for second-line treatment of SCLC does not appear to cause anthracycline-related cardiomyopathy. [Table: see text] [Table: see text]