Pixantrone shows promise for relapsed non-Hodgkin lymphoma
MedWire News: Pixantrone dimaleate, given as a single-agent salvage therapy, may be a treatment option for heavily pretreated patients with relapsed or refractory aggressive non-Hodgkin lymphoma, results of a randomized phase III clinical trial show.
Fourteen (20%) of 70 patients assigned to receive treatment with pixantrone achieved a complete or unconfirmed complete response at the end of treatment according to an independent assessment panel. This compared with just four (5.7%) of 70 patients assigned to the investigators' comparator agent of choice, a difference that was statistically significant.
The patients, recruited from 66 hospitals in Europe, India, Russia, South America, the UK, and the USA, had all relapsed at least twice and had received a previous regimen that included an anthracycline combination.
The study findings, reported by Ruth Pettengell (University of London, UK) and colleagues in The Lancet Oncology, also show that median progression-free survival was significantly longer among the patients who received pixantrone compared with those who received a comparator drug (vinorelbine, oxaliplatin, ifosfamide, etoposide, mitoxantrone, or gemcitabine), at 5.3 versus 2.6 months.
Toxicity was "manageable" say the researchers. Overall adverse event rates were similar between the pixantrone and comparator groups (97.1 vs 91.0%), but more patients had a grade 3 or 4 event - most commonly neutropenia, leucopenia, and thrombocytopenia - in the pixantrone group (76.5%) than in the comparator group (52.2%).
However, the researchers point out that patients given pixantrone stayed on treatment longer than controls, and were therefore at risk for adverse events for a longer period of time.
In an accompanying commentary, Fernando Cabanillas (Hospital Auxilio Mutuo, San Juan, Puerto Rico) notes that pixantrone, a drug structurally related to the anthracyclines but with reduced cardiotoxicity, was recently rejected by the US Food and Drug Administration (FDA) because the trial "was not flawlessly executed," and the investigators did not seek FDA guidance before stopping recruitment early due to low numbers.
The European Medicines Agency (EMA), on the other hand, granted approval on the condition that data on patients previously treated with rituximab, which is now standard of care for patients with relapsed aggressive non-Hodgkin lymphoma, be provided.
The researchers report that just over 50% of patients had received rituximab before enrolment, and although they did not respond as well to pixantrone as patients who had not received rituximab, the response was still better than treatment with a comparator drug.
Notwithstanding the limitations of the small sample size, Cabanillas says the data "look promising," and that the EMA "made a wise decision to grant this agent approval."
By Laura Cowen