NEW YORK (
(CELG - Get Report)
phase III trial of Abraxane in pancreatic cancer will be a statistical success, my research predicts. The trickier question is whether or not the Abraxane survival benefit observed in the trial will be clinically meaningful. I think it will.
Results from the Abraxane pancreatic cancer study are expected later this quarter.
Acquired through Celgene's $2.9 billion purchase of Abraxis BioScience in 2010, Abraxane is an albumin-bound formulation of the chemotherapy drug paclitaxel. Abraxane generates annual revenue of $450 million as a treatment for breast cancer but hasn't lived up to investor expectations thus far. That may be changing. Earlier this month, Celgene unexpectedly reported positive Abraxane data from a phase III study in melanoma. Last week the FDA allowed expansion of the drug's label to include treatment of non-small cell lung cancer (NSCLC). Both of these indications are likely modest commercial opportunities and investor expectations seem low.
Pancreatic cancer is another matter.
In late 2011, investigators from Abraxis published results from a single-arm phase I/II study of Abraxane plus gemcitabine in front-line metastatic pancreatic cancer in the
Journal of Clinical Oncology
. These data showed an impressive 48% overall response rate with median progression-free survival of 7.9 months and median overall survival of 12.2 months. These data compare favorably to historical results for gemcitabine monotherapy in pancreatic cancer -- progression-free survival of 3.5 months and overall survival in the range of 6-7 months.
Based on the positive phase I/II data, Celgene initiated a randomized phase III trial of Abraxane plus gemcitabine compared to gemcitabine monotherapy. Originally slated to enroll 630 front-line pancreatic cancer patients, investigators increased the trial's size to 842 patients in the fall of 2010. As far as I can tell, this is the largest clinical trial ever in pancreatic cancer. The primary endpoint is overall survival.
Even if the combination meaningfully underperforms earlier results in the Phase III study and single-agent gemcitabine outperforms expectations, it seems likely that Abraxane will show a statistically significant, 2-3 month survival benefit over the control group.
The more challenging questions about Abraxane have to do with the drug's tolerability and whether or not any observed survival benefit will be clinically meaningful. Tarceva was approved in pancreatic cancer but is rarely used because the drug was shown to improve survival by a paltry 12 days over gemcitabine monotherapy.
Likewise, some physicians suggest that in order for Abraxane to garner widespread use in pancreatic cancer, it will have to outperform FOLFIRINOX, a four-drug chemotherapy regimen.
It's hard for me to believe that physicians wouldn't consider a 2-3 month survival benefit clinically meaningful, but the concern about the drug's absolute survival seems plausible.
Let's take a closer look at FOLFIRINOX.
In the FOLFIRINOX study, 48% of patients survived for one year and median overall survival reached 11.1 months. My "worst reasonable case" estimate -- which excludes outright failure -- is that Abraxane-gemcitabine patients will report a median overall survival of 9.8 months. I think it's more likely that the respective survival duration for Abraxane and FOLFIRINOX will be similar.
With cancer drugs, efficacy is usually regarded as more important than safety given the life-threatening nature of the disease, but FOLFIRINOX's toxicity is an issue to consider.