The recent phase 3 PIX306 trial (EU Clinical Trials Register Number: 2012-001790-86) evaluating the combination of pixantrone plus rituximab (PIX+R) in comparison with gemcitabine plus rituximab (GEM+R) in treatment of relapsed, aggressive B-cell non-Hodgkin lymphoma (NHL) did not meet its primary end point. The study’s results were reported in the British Journal of Haematology.
The trial examined treatment outcomes in 312 patients with diffuse large B-cell lymphoma (DLBCL) or grade 3 follicular lymphoma (FL) who were randomly assigned 1:1 to receive either PIX+R or GEM+R for a maximum of 6 cycles of treatment. Enrolled patients had experienced relapse after 1 or more prior treatments containing rituximab, and they were not candidates for stem cell transplantation. A significant difference in progression-free survival (PFS) between groups was the primary study end point.
With a maximum study follow up of 96 weeks, median PFS for patients on PIX+R was 7.3 months (95% CI, 5.2-8.4), compared with 6.3 months (95% CI, 4.4-8.1) for patients receiving GEM+R. The hazard ratio (HR) for this comparison was 0.85 (95% CI, 0.64-1.14; P =.28) in intention-to-treat analysis.
The overall response rates were 61.9% (95% CI, 53.8%-69.6%) with PIX+R and 43.9% (95% CI, 36.0%-52.1%) with GEM+R. Complete response was seen in 35.5% (95% CI, 28.0%-43.6%) of patients on PIX+R and 21.7% (95% CI, 15.5%-28.9%) on GEM+R.
Most patients had 1 or more grade 3 to 4 adverse events, including 85.0% of patients on PIX+R and 88.6% of patients on GEM+R. Cardiac adverse events were reported in 39.2% of patients on PIX+R and 36.9% on GEM+R. Reportedly, deaths related to treatment-emergent adverse events occurred in 14 patients on PIX+R and 8 patients on GEM+R.
Although this analysis did not favor treatment with PIX+R, the study investigators wrote in their report that “the results demonstrate that pixantrone is an active agent in aggressive NHL with a predictable safety profile in combination with rituximab in this patient group.”
1. Pettengell R, Długosz-Danecka M, Andorsky D, et al. Pixantrone plus rituximab versus gemcitabine plus rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma not eligible for stem cell transplantation: a phase 3, randomized, multicentre trial (PIX306) [published online December 27, 2019]. Br J Haematol. doi:10.1111/bjh.16255