The phase 3 EXTEND PIX301 trial, which will be reviewed by the US Food and Drug Administration’s (FDA) Oncologic Drugs Advisory Committee (ODAC) in the near future, is raising serious questions among members regarding the efficacy and safety of pixantrone.
The drug is intended to treat non-Hodgkin’s lymphoma (NHL) that has resisted at least 2 other treatments.
Among multiple concerns, the trial only included 40% of the original 320 participants that were to be enrolled.
A possible explanation is that third-line patients wanted to use multi-agent chemotherapy or supportive care. Regardless of the reason, ODAC members are unsure if 140 participants can provide enough evidence for reliable conclusions.
Twenty percent of patients receiving pixantrone achieved complete responses (CR) or unconfirmed complete responses (CRu), compared to less than 6% in the comparator group (P=0.021).
However, it has been noted that if only 2 fewer patients achieved CR or CRu, the data would not be statistically significant (P=0.06).
The comparator arm was the doctors’ choice of other single-agent chemotherapy.
Grade 3-4 serious adverse events, including neutropenia, anemia, leukopenia, and thrombocytopenia, were higher in the pixantrone arm (77% versus 52%).
There were 12 deaths from adverse events in the pixantrone arm of the study from cardiac failure, infection, respiratory failure, and other causes.
There were only 5 deaths from adverse events in the comparator arm, suggesting that pixantrone is cardiotoxic, although the FDA did not claim to be able to draw conclusions relative to other NHL drugs.
The committee moved 2 patients from the pixantrone arm of the study to a different response category and 1 from the comparator arm after reviewing radiology scans. No bias was detected during the review.
ODAC was scheduled to meet Wednesday, February 10, but the meeting was postponed due to heavy snow.
The EXTEND PIX301 trial is sponsored by Cell Therapeutics, the company developing pixantrone.
