Phase III Extended Trial Finds Pixantrone Favorable Compared with Commonly Used Chemotherapies in Aggressive NHL

New Orleans, LA — Single-agent pixantrone, an investigational agent, showed encouraging third-line responses, duration of responses, and progression-free survival (PFS) compared with other single-agent chemotherapies in patients with relapsed aggressive non-Hodgkin lymphoma (NHL) in the phase III, randomized, open-label, multicenter EXTEND trial. In the study, patients with relapsed/refractory NHL treated with pixantrone achieved significant increases in complete response (CR) and overall response (ORR) and demonstrated a positive trend in overall survival (OS) compared with other chemotherapy agents, according to Ruth Pettengell, MD, of St. Georges Hospital in London, who presented these results at a poster session. “An anthracycline with reduced cardiotoxicity that can be used for salvage therapy of aggressive NHL meets a significant unmet medical need,” she said.

Pixantrone is a novel aza-anthracenedione related to mitoxantrone and anthracyclines, but its structure differentiates it from anthracyclines and related chemotherapies. Although anthracyclines are effective first-line treatments for a number of cancers, they have a lifetime risk of cumulative cardiotoxicity. Pitoxantrone has been designed to avoid cardiotoxicity and, unlike anthracyclines, it can be administered via a peripheral vein.

The study enrolled 140 patients who failed on at least 1 prior anthracycline-containing regimen and failed 2 prior treatment regimens for relapsed aggressive NHL. Patients were randomized to receive up to 85 mg/m² of pixantrone on days 1, 8, and 15 of a 28-day cycle for up to 6 cycles (n = 70) or to a different single-agent comparator (n = 70) at the discretion of the treating physician. Comparator drugs included vinorelbine (Navelbine), oxaliplatin, ifosfamide, etoposide, or mitoxantrone; in the United States, only gemcitabine (Gemzar) and rituximab (Rituxan) were permitted. All patients were followed for up to 18 months after receiving the last treatment cycle. The primary endpoint was independent assessment of complete response/unconfirmed complete response (CR/Cru).

In total, 96% of patients received treatment, with patients in the pixantrone arm receiving a median number of 4 cycles versus 3 cycles in the comparator group. Approximately one-third (32.4%) of patients in the pixantrone group received all 6 treatment cycles compared with 28.4% of patients in the comparator group.

According to an intent-to-treat analysis, CR/CRu at the end of 6 months of treatment was 20% for the pixantrone group, which was statistically superior to the overall 5.7% rate of CR/CRu achieved by comparator drugs (P = .021). The overall response rate (ORR) was also significantly superior in the pixantrone group, at 40% versus 14.3%, respectively (P = .001), as was the percentage of patients achieving a durable objective response of ≥4 months (25.7% vs 8.6%, respectively; P = .012). Median progression-free survival (PFS) was 4.7 months for the pixantrone group versus 2.6 months for the comparator arm (P = .007).

After a minimum 9 months’ of follow-up, CR/Cru was 25.7% for the pixantrone group versus 7% for the comparator arm (P = .005), and ORR was 40% versus 14.3% (P = .001). Median PFS was 5.6 months for the pixantrone arm versus 2.6 months for the comparator group (P = .002). Median OS was 10.2 months versus 6.9 months, favoring the pixantrone arm, a difference that was not statistically significant. The pixantrone arm also achieved a better rate of 1-year survival, at 45% compared with 35% for the comparator arm. Subgroup assessments also favored pixantrone over comparator drugs, including prior exposure to anthracyclines, rituximab (treated or not treated), International Prognostic Index score, NHL diagnosis (relapsed or refractory), and age.

Pixantrone was tolerable in these heavily pretreated patients, although more patients in the pixantrone group experienced grade 3-4 neutropenia (41.2% vs 19.4%, respectively), leukopenia (23.5% vs 4.5%, respectively), and febrile neutropenia (7.4% vs 3%, respectively). Serious cardiac adverse events occurred in 8.8% of patients in the pixantrone group versus 4.5% in the comparator arm. Dr Pettengell noted that the incidence of serious cardiac events for cumulative median doxorubicin-equivalent doses of 535 mg/m² were lower than expected in the pixantrone-treated group. ASH Abstract 1677.

This study was funded by Cell Therapeutics.

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