8523 Background: Currently, treatment options for multiply relapsed aggressive NHL are limited, and response rates are disappointing. Pixantrone, a novel aza-anthracenedione with structural similarities to mitoxantrone, has potentially reduced cardiotoxicity and has demonstrated promising clinical activity in phase II studies in heavily pretreated NHL patients.
METHODS
PIX301 was a controlled, multicenter, open-label phase III study of ≥ third-line treatment of relapsed aggressive (de novo or transformed) NHL. All patients were required to have received ≥ 1 prior anthracycline-containing regimen, with the cumulative doxorubicin-equivalent dose limited to ≤ 450 mg/m2. Randomization was to pixantrone 85 mg/m2 on days 1, 8 and 15 of 28-day cycles, for up to 6 cycles, or to investigator's choice of a single-agent comparator (vinorelbine, oxaliplatin, ifosfamide, etoposide, or mitoxantrone; in the US only, gemcitabine and rituximab were permitted). The primary study endpoint was CR/CRu rate. Secondary objectives included safety, OS, and ORR. Originally planned to enroll 320 patients, PIX301 was amended to 140 patients due to slow enrollment.
RESULTS
140 patients (70 per arm) were randomized. Median age was 60 on the pixantrone arm, 58 on the control arm; patients on both arms had received a median of 3 prior chemotherapeutic regimens. Based on independent review in the ITT population, the CR/CRu rate in patients treated with pixantrone was significantly higher than in those receiving other agents (20.0% vs. 5.7%, p-value = 0.02), and there were no CRs in the control group compared to 8 CRs in the pixantrone group.
CONCLUSIONS
In this study, single-agent therapy with pixantrone achieved significantly superior CR/CRu and ORR rates in ≥ third-line treatment of relapsed/refractory aggressive NHL. [Table: see text] No significant financial relationships to disclose.