Phase 3 Trial of Pixantrone in Treating Non-Hodgkin Lymphoma Patients

Olrando—Compared with other chemotherapy agents, pixantrone proved more effective in treating patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to a randomized, controlled, international, multicenter, open-label, phase 3 trial presented at the ASH meeting. Pixantrone had a superior complete remission rate (CRR), superior overall response rate (ORR), superior progression-free survival (PFS), and showed a positive trend in overall survival (OS). The poster was titled Phase III Trial of Pixantrone Dimaleate Compared with Other Agents as Third-Line, Single-Agent Treatment of Relapsed Aggressive Non-Hodgkin Lymphoma (EXTEND): End of Study Results. The US Food and Drug Administration has not approved a drug to provide reliable and durable efficacy for patients with aggressive NHL who relapse after ≥2 lines of therapy. Pixantrone, a novel aza-anthracenedione structurally similar to miloxantrone and anthracyclines, minimally promotes formation of reactive oxygen species. Animal models found that pixantrone significantly reduced cardiotoxicity compared with miloxantrone and doxorubicin. In phase 1 and 2 trials of pixantrone as a single agent and in combination showed that the drug led to substantial response rates in patients with aggressive or indolent NHL. Although patients had prior ≤450-mg doxorubicin exposure, there was also a low incidence of grade 3 and 4 cardiac disorders. The phase 3 study enrolled 140 patients ≥18 years of age with histologically confirmed aggressive NHL who had a relapse after ≥2 chemotherapy regimens. Inclusion criteria were an Eastern Cooperative Oncology Group performance status between 0 and 2, prior cumulative dose of <450 mg/m2 of doxorubicin or a <50% baseline left ventricular ejection fraction, no clinically significant cardiovascular abnormalities, and no serious intercurrent infection. There were 2 groups, with 70 patients receiving 85 mg/m2 of pixantrone and the remaining 70 patients receiving standard doses and regimens of other drugs, including vinorelbine, oxaliplatin, ifosfamide, etoposide, or mitoxantrone. The groups were followed for 18 months after last treatment. Patients receiving pixantrone had a higher median number of treatment cycles and an approximately 1-month longer median duration of treatment compared with the other group. At the end of treatment, the pixantrone group had a CRR of 20% (n=14) compared with 5.7% (n=4) in the other group (P=.021), while patients taking pixantrone had an ORR of 37.1% (n=26) compared with 14.3% (n=10) for the other group (P=.003). After the 18-month follow-up, 3 more patients who took pixantrone and 1 additional patient in the other group achieved CRR (P=.009), while 2 more patients in the pixantrone group had an OR (P=.001). During those 18 months, neither group had further treatment. The pixantrone group also had a median duration of CRR of 9.6 months, while the other groups had a median duration of CRR of 4.0 months (P=.081). The pixantrone group also had a 40% improvement in PFS and a 21% improvement in OS versus patients in the other group, the researchers said.