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Single-Agent Pixantrone Effective for Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma: Presented at ASH

By Betty S. Riggs

NEW ORLEANS, LA -- December 6, 2009 -- Among several third-line agents evaluated for the treatment of patients with relapsed/refractory non-Hodgkin's lymphoma (NHL), pixantrone dimaleate demonstrated superiority, with significantly better response and a notable 1-year survival rate.

These are the interim results of the EXTEND study presented here December 5 at the American Society of Hematology (ASH) 51st Annual Meeting and Exposition.

In this randomised, multicentre, controlled study, adult patients with aggressive (de novo or transformed) NHL who had relapsed after at least 2 prior chemotherapy regimens (including at least 1 prior anthracycline-containing regimen) were treated with either pixantrone 85 mg/m2 for up to 6 cycles (n = 70) or with the investigator's choice of a single-agent comparator (n = 70) given at standard dosages. Comparator agents included vinorelbine, oxaliplatin, ifosfamide, etoposide, and mitoxantrone, as well as gemcitabine or rituximab where permitted.

Patients in both groups were followed for 18 months after last treatment. The primary endpoint was the combined complete response (CR)/CR unconfirmed (CRu) rate, which was evaluated by an independent assessment panel. Other efficacy endpoints evaluated included overall response rate (ORR), responses lasting >=4 months, progression-free survival (PFS), overall survival (OS), and safety.

Ruth Pettengell, MD, PhD, St Georges Hospital, London, United Kingdom, reported the interim findings, which include the results from the treatment period and updated results from a minimum 9-month follow-up period.

Patients in the pixantrone group received a median of 4 treatment cycles, compared with a median 3 cycles for the comparator group. The CR/CRu rate, based on an intent-to-treat analysis, was nearly 4 times higher in the pixantrone group: 20.0% versus 5.7% for the comparator group (P = .021). Likewise, the ORR for the pixantrone group was significantly higher than the ORR for the comparator group (37.1% vs 14.3%; P = .003).

At 9 months of follow-up, the percentage of patients with CR/CRu for the pixantrone group was 25.7% versus 7.0% for the comparator (P =.005), and the ORR was 40% and 14.3%, respectively (P = .001). The percentage of patients with objective responses lasting at least 4 months was 25.7% for the pixantrone group compared with 8.6% for the comparator group (P = .012).

Patients treated with pixantrone remained free of disease progression for a median of 4.7 months, compared with 2.6 months for the comparator group [HR (95% confidence interval[CI]) = 0.60 (0.41-0.88), log rank P = .007]. At the end of 9 months' follow-up, the median PFS in the pixantrone group was 5.6 months compared with 2.6 months for the comparator [HR (95% CI) = 0.56 (0.39-0.81), log rank P = .002].

The 1-year OS was 44% for the pixantrone group compared with 35% for the comparator (HR = 0.35, log rank P = .82). While not fully mature, Dr. Pettengell said that the pixantrone survival rate is noteworthy for this group of patients who had a median disease duration of nearly 3 years and who had been treated with multiple prior chemotherapy regimens.

More patients in the pixantrone group (75.0%) had a grade 3/4 adverse event than in the comparator group (50.7%). Neutropenia and leucopenia occurred more commonly in the pixantrone group (41.2% and 23.5%, respectively) than the comparator group (19.4% and 4.5%, respectively). Anaemia occurred more commonly in the comparator group (13.4%) than in the pixantrone group (5.9%). The percentage of patients with serious cardiac events was 8.8% in the pixantrone group compared with 4.5% for the comparator group.

Based on this study, treatment of patients with relapsed aggressive NHL with single-agent pixantrone achieved superior efficacy compared with other single-agent chemotherapeutic agents.

The safety profile was encouraging, with a lower than expected incidence of serious cardiac events.

This study was sponsored by Cell Therapeutics, Inc.

[Abstract title: Phase III Trial of Pixantrone Dimaleate Compared With Other Agents as Third-Line, Single-Agent Treatment of Relapsed Aggressive Non-Hodgkin's Lymphoma (EXTEND): Results From the Treatment and Follow-up Periods. Abstract 1677]

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