9/26/2013
When was the last time you saw a new treatment for pancreatic cancer? I'd be willing to bet a long time, right?
In 2005, erlotinib (Tarceva), in combination with gemcitabine (Gemzar), was approved for locally advanced, unresectable, or metastatic pancreatic cancer.1 Not since then have we had anything new to offer patients with this advanced disease -- until now.
The FDA has just approved the use of Abraxane in combination with gemcitabine as first-line therapy for metastatic pancreatic adenocarcinoma. You may be familiar with Abraxane for its long-time use in metastatic breast cancer and more recently for its indication in treating non-small-cell lung cancer.
Abraxane is classified as a microtubule inhibitor. Specifically, it
promotes the assembly and stability of microtubules within the cell,
essentially inhibiting the disassembly of the structure and thereby
inhibiting cell replication.2Also, Abraxane belongs to the taxane family, which includes well-known drugs like paclitaxel (Taxol) and docetaxel (Taxotere). Taxane drugs are derived from the Pacific yew tree and are notorious for their potential to cause hypersensitivity reactions with administration. However, Abraxane offers the antineoplastic benefits of the taxane family with a reduced risk of allergic reaction. This is because Abraxane is protein-bound paclitaxel, meaning particles of paclitaxel are bound to albumin for delivery of the drug.
The most recent FDA approval for Abraxane followed a multicenter/multinational study of 861 previously chemotherapy-naïve patients comparing Abraxane plus gemcitabine versus gemcitabine alone; 431 patients were randomized to the Abraxane/gemcitabine arm, and 430 to gemcitabine monotherapy.
Those receiving both drugs were given Abraxane 125 mg/m2 followed by gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle. Those receiving gemcitabine alone received 1,000 mg/m2 for seven weeks on, one week off with cycle one and thereafter were treated three weeks on, one off. In both arms, therapy was continued until disease progression or unacceptable toxicity. Study endpoints included overall survival (OS), progression free survival (PFS), and overall response rate (ORR).
The study results showed Abraxane/gemcitabine offered patients a statistically significant advantage in OS (8.5 months versus 6.7). There was also improvement in PFS (5.5 months versus 3.7) and ORR (99 percent versus 31 percent).
As you read those statistically significant numbers, what are your initial thoughts? You might be thinking how great it is that researchers have found something to improve survival in the metastatic pancreatic patient setting. I would agree with this, and I appreciate the statistical significance of the study, including the large sample size. However, when I crunch the numbers, I'm personally left thinking, "Just a two-month benefit in survival time?" I suppose anything like this should be looked upon as a success, considering most patients who present with pancreatic cancer have advanced disease at diagnosis and will likely die within a few years. In fact, of the 861 study patients, 692 had died at the 36-month mark.
Overall, this new approach to treating advanced pancreatic cancer patients is a step in the right direction. However, for the future, I'd like to see erlotinib/gemcitabine compared to Abraxane/gemcitabine. This would be a more interesting comparison study in terms of which offers the greater benefit. Even better still would be a new targeted therapy specifically for pancreatic cancer.
As it stands on the NCI Clinical Trials website, there is no pancreatic cancer-specific trial looking at a new novel agent. Perhaps some of you out there are aware of new drugs coming down the pipeline. For the rest of you, what are your thoughts on using Abraxane/gemcitabine? Have any of you begun doing this in your practice?
References:
- National Cancer Institute: FDA Approval for Erlotinib Hydrochloride.
- Abraxane Drug Information. Pharmacology. Accessed September 25, 2013 from UpToDate.
No comments:
Post a Comment