It's been over two years since I reported the details from a positive trial for Abraxane (albumin-bound paclitaxel) as a weekly treatment combined with carboplatin and compared with standard "solvent-based" Taxol (paclitaxel) along with carboplatin.  While positive for showing a 8% difference in response rate, which was the primary endpoint, it didn't show a significant difference in overall survival (OS), as revealed in the completed publication of the trial earlier this year.  Beyond these very basic results, there have been some notable positive features of Abraxane from the trial:

- Patients with squamous NSCLC appeared to benefit more significantly, with a response rate of 41% vs. 24% on the carbo/Abraxane vs. carbo/Taxol arms, respectively, there there was no difference in survival between the two arms

- Survival was significantly longer in the subset of patients age 70 or older (median OS 19.9 vs. 10.4 months, P = 0.009) and in patients enrolled from North America (12.7 vs. 9.8 months, P = 0.008).

- Abraxane doesn't require steroid premedication that is required before Taxol and can be challenging for many patients 

While Abraxane was relatively rarely used in lung cancer before now, as a relatively expensive medication  without a striking benefit over other alternatives and that hasn't been FDA approved, the situation changes today for US-based patients, since the FDA voted to approve it as a first line treatment along with carboplatin for patients with advanced NSCLC.

What does this mean? What should this mean?

People who have read my posts and comments in the discussion forums here at GRACE have seen that I have been less than wildly enthused about Abraxane.  It's not that I haven't felt it represents a modest improvement, but rather that the striking cost differential for Abraxane vs. standard "solvent-based" Taxol seemed to me to be disproportionate to the more modest incremental benefit in how it helps patients.  But I'd confess now that I have more mixed feelings now and would probably be inclined to favor Abraxane for a reasonable subset of my own patients.

First, I need to acknowledge the inconsistency in my being rather fond of Alimta (pemetrexed) for non-squamous NSCLC while being critical of Abraxane based on cost.  Abraxane is expensive but comparable to Alimta, and I and most other lung cancer specialists have readily used Alimta for appropriate patients, often for very long periods of time (and therefore at a considerable cost).  It's not that far cheaper chemo agents -- such as standard Taxol, Taxotere (docetaxel), Gemzar (gemcitabine), or (Navelbine (vinorelbine) -- wouldn't be an appropriate option. It's just that the overall balance of efficacy and tolerability for Alimta has made it somewhat of a darling of myself and many other lung cancer specialists. But that has also required us to turn a blind eye to the cost of the regimen  -- especially if we added Avastin (bevacizumab) to the regimen!

I'd personally be most inclined to use Abraxane in patients with squamous NSCLC, since that's a group in whom the response rate appeared more provocatively superior.  In this group, I have historically favored a platinum/gemcitabine combination, since it's also often very well tolerated and doesn't require steroids , and doesn't lead to much hair loss in most patients.  Typically, I've favored cisplatin/gemcitabine for many of my most fit patients with squamous NSCLC, since there's some modest evidence that outcomes are marginally better with cisplatin than with carboplatin, but a large proportion of patients who start with cisplatin find it very difficult to tolerate.  And while the carbo/gemcitabine regimen is typically easier for patients to feel well on, it often causes very significant drops in blood counts that can make it difficult to continue on a regular schedule and without ongoing dose reductions.   These problems with low blood counts tend to be especially common in older patients.  So while Abraxane is associated with hair loss, it has the appeal of being a generally well tolerated agent to combine with carboplatin without severe drops in blood counts and that doesn't require steroid premedication (a relatively minor factor in my experience, but a plus), that may enable my patients to receive treatment as planned, with fewer dose delays and reductions than what I've historically done.

I'm intrigued by the findings from the subgroup analysis that indicated more favorable results in patients in North America and also in patients 70 and older, but it's important to highlight that each of these groups represented only about 15% of the entire trial population.  The finding specific to North America may be related to practice patterns of giving more post-trial therapy after progression, or some other unmeasured factor, but it may also be a random finding that doesn't hold up to more careful testing.  As for the elderly, it may be that the weekly chemo regimen with Abraxane is a better choice than a bigger slug of Taxol once every three weeks.  There will be subsequent research on this question (including by GRACE faculty member Dr. Jared Weiss), but in the meantime I'd just consider Abraxane to be a very fine choice older patients, and arguably a preferred one for older patients with a squamous NSCLC, even in the absence of more definitive evidence.

One other major factor will be whether payers readily cover Abraxane or indicate a clear favoring of a less expensive alternative.  Historically, they haven't tended to dissuade oncologists from an FDA approved regimen, but I'll admit that I've had far more input about giving a more expensive agent like XGEVA (denosumab) vs. Zometa (zoledronate) in the last 6 months than ever before.  Sad to say, but we may well find that a physician's preference becomes less relevant as we become subjected to pressure to follow payer-imposed limitations.

What do you think? Are you impressed that Abraxane adds true, meaningful benefit and a new treatment option, or is it a slightly improved version of Taxol with a very big markup in price?