Ziopharm designed PICASSO-3 with the assumption that STS patients treated with doxorubicin alone would yield a median PFS of 4.3 months, or equal to the results seen in PICASSO. The study was powered so that a median PFS benefit of three months or more for patients treated with palifosfamide-doxorubcin (median PFS of 7 months-plus) will produce statistically significant results. Expressed another way, Ziopharm is aiming for a 40% reduction in the relative risk of tumor progression, which if achieved, may also produce a survival benefit.
I believe the addition of palifosfamide to doxorubicin is likely to demonstrate some improvement over doxorubicin alone in STS patients in PICASSO-3. I'm less confident about results replicating what was seen in PICASSO, meaning the study could fail to achieve the primary endpoint with statistical significance.
Given the lack of additional treatment options for STS patients, Ziopharm is likely to seek U.S. approval of palifosfamide even if PICASSO-3 results only show a trend favoring the drug. An absolute benefit in PFS of at least two months coupled with no additional toxicity might be viewed favorably by an FDA advisory panel and could lead to FDA approval.
Chaudhry has no position in Ziopharm.Follow Aafia Chaudjry on Twitter.