Many observers have been puzzled by the presentation at the American Society of Clinical Oncology meeting in Chicago of a study which claimed that two new breast cancer drugs - Celgene Corp’s Abraxane and Bristol-Myers Squibb’s Ixempra - were no better than paclitaxel.
The Phase III study enrolled 799 patients with locally advanced or metastatic breast cancer who were randomised to receive one of the three therapies - paclitaxel (the standard of care), Abraxane (nanoparticle albumin bound -'nab' - paclitaxel) or Ixempra (ixabepilone) - on a weekly basis with each cycle consisting of three weeks of treatment followed by a one-week break. Some 98% of patients also received Roche's Avastin (bevacizumab), which had its approval for breast cancer revoked by the US Food and Drug Administration in November 2011.
The data from the study, presented at ASCO by lead investigator Hope Rugo at the University of California, San Francisco, stated that median progression-free survival was 10.6 months for those receiving paclitaxel, 9.2 months for nab-paclitaxel, and 7.6 months for ixabepilone.
Grade 3 or 4 non-haematologic toxicities were also lowest in the paclitaxel arm, including sensory neuropathy (16% versus 25% for both experimental arms), while haematologic toxicities were lowest in the ixabepilone arm, and highest for Abraxane (12% versus 51%), compared to paclitaxel (21%). Dr Rugo said that the study "demonstrates that we should not simply assume that newer drugs are always better than the standard therapies".
150mg dose used in study never used in practice
However the findings, particularly in the Abraxane arm, caused raised eyebrows among oncologists at the meeting. The dose of the Celgene drug used was 150mg, well above the 100mg for which Abraxane is approved in over 40 or so countries, and when asked by PharmaTimes World News as to why the higher dose was selected, Dr Rugo noted that it had been used in a Phase II trial by the company.
However, Brian Gill, head of global corporate communications at Celgene, noted that there is only one trial to date "that is a true head-to-head study between Abraxane and paclitaxel". Those results showed statistical significance in time to disease-progression, PFS and overall survival. He added that "it was very curious to see why the decision was made to use the 150mg rather than the successful dose on the label" and expressed his surprise over the use of Avastin.
While Avastin is "a wonderful drug," lots of peer-reviewed publications note that the Roche drug, used in combination with other therapies, exacerbates toxicities, he told PharmaTimes World News. Between using the higher dose with Avastin, it appears that about 50% of patients actually discontinued the therapy in the latest study.
William Sikov of the Brown University School of Medicine, said he had no problems about the conduct of the study but questioned its design in terms of the 150mg dose, which would have led to missed and delayed doses in that arm. He was surprised by the broad statement that patients can do equally well on paclitaxel than Abraxane, a stance he felt was "contradictory" given that the latter is highly effective when used at the right dose.
When asked by PharmaTimes World News whether the 150mg dose was ever used in clinical practice, Dr Sikov gave a clear 'no', although occasionally 125mg is used. He noted that the 150mg used in the Phase II study had appeared to be the most active, although toxic as well, "but it is very different going from a 75-patient Phase II study to a 200-plus patient trial".
Other breast cancer specialists that spoke to this publication were also surprised that ASCO had chosen to highlight this study, with one suggesting that while making a case for the use of cheap generics is a valid one, in the case of Abraxane versus pacitaxel, the argument falls down.
Celgene has recently stated that peak sales of Abraxane, which is also being studied in lung and pancreatic cancer, as well as melanoma, could be in the region of $1.5 billion, with as much as a quarter of that coming from pancreatic cancer.