Cell Therapeutics, Inc. (CTI) has announced results from sub-set analyses of data from the Phase 3 EXTEND, or PIX301, clinical trial of PIXUVRI® (pixantrone).
The analyses evaluated the efficacy of PIXUVRI in the subset of patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL), as confirmed by central independent pathological review, who had failed 2 or 3 prior treatment regimens (3rd and 4th line in the licensed patient population).
Compared to physicians' choice of other agents given as monotherapy, single agent PIXUVRI resulted in 30 percent of patients who had previously received rituximab achieving a complete or unconfirmed durable complete response lasting on average 9.5 months with 67 percent of patients surviving at 2 years.
In contrast, only 5.6 percent of patients in the comparator arm achieved an unconfirmed complete response. The benefit of PIXUVRI has not be established in patients when used as 5th-line or greater chemotherapy.
The analyses were presented by Professor Ruth Pettengell, M.D., St. George's Hospital, at the 18th Congress of the European Hematology Association (EHA) held June 13-16, 2013 in Stockholm, Sweden.
Abstract #P310: Pixantrone monotherapy in histologically confirmed, relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial. Poster session, Friday, June 14, 5:45 to 7:00 p.m. CEST.
"PIXUVRI is the first medicinal product approved in the E.U. for treatment of patients with aggressive B-cell NHL," said Ruth Pettengell, M.D., of St. George's Hospital, University of London, the lead investigator for the EXTEND trial. "These subset analyses support PIXUVRI's use and benefit as a 3rd and 4th line treatment, whether or not the patient was previously exposed to rituximab. Prior to PIXUVRI, treatment options were limited to palliative therapy or clinical trials. PIXUVRI may provide the ability to re-introduce effective salvage therapy even after patients fail standard aggressive second line treatment."
Additional highlights from these post-hoc analyses include:
• PIXUVRI demonstrated superior complete response rates and progression-free survival (PFS) in all the subgroups analyzed.
• In patients who had aggressive B-cell histology as determined by site pathologists only, who had failed two or three prior lines of therapy, PIXUVRI was more efficacious than physicians' choice of monotherapy, both in patients who had received prior rituximab and those who did not. Among the patients whose histology was confirmed by the panel and who had received rituximab prior to randomization, response rates and PFS were as follows for PIXUVRI compared to physicians' choice of therapy, respectively: CR/CRu=30.0 percent vs. 5.6 percent; ORR=45.0 percent vs. 11.1 percent; PFS=5.4 vs. 2.8 months.
• In patients with aggressive B-cell NHL, there was a 48 percent improvement in PFS that were confirmed by central review compared to 15 percent improvement in PFS based on site determination. This suggests that the superior efficacy of PIXUVRI in the patients who had previously received rituximab was not due to inclusion of a disproportionate share of patients who could not be confirmed as having aggressive B-cell NHL on central pathological review.
In May 2012, the European Commission granted conditional marketing authorization for PIXUVRI as a monotherapy for the treatment of adult patients with multiply relapsed or refractory aggressive NHL based on the results of the EXTEND, or PIX301, pivotal randomized Phase 3 clinical trial.
The benefit of PIXUVRI treatment has not been established in patients when used as fifth line or greater chemotherapy in patients who are refractory to last therapy. The Summary of Product Characteristics (SmPC) has the full prescribing information, including the safety and efficacy profile of PIXUVRI in the approved indication.
The SmPC is available at www.pixuvri.eu. CTI is currently accruing patients into a Phase 3 trial comparing PIXUVRI and rituximab with gemcitabine and rituximab in the setting of aggressive B-cell NHL. PIXUVRI does not have marketing approval in the United States.