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Positive trial for Abraxane in NSCLC: Follow-up From ASCO

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Three months ago, I discussed the press release from Abraxis reporting that the phase III trial of carbo/Abraxane (nanoparticle albumin-bound paclitaxel) vs. carbo/taxol (paclitaxel) showed a significant benefit for higher response rate in the Abraxane arm. Carboplatin was given one day every three weeks, as was taxol, and Abraxane was given every week (no break). We received more information, though not a lot more, with the presentation at ASCO earlier this month.

The trial enrolled 1053 patients with previously untreated advanced NSCLC, the majority from Russia and the Ukraine, to either standard carbo/taxol or the albumen-bound form that doesn’t require steroid pretreatment and has a somewhat different toxicity profile. We don’t have progression-free survival (PFS) or overall survival (OS) data yet, but we did get some numbers for response rates. Specifically, according to a pre-planned independent radiologist review, the carbo/Abraxane arm had a RR of 33%, compared with 25% for carbo/taxol. The numbers were a little higher in the investigator-reported numbers, but with essentially the same difference (37% vs. 30%).

abraxane-trial-rr-by-all-histologies

(click on image to enlarge)

What was more interesting, in my opinion, was that the breakdown by histology showed that, at least according to the independent radiology reviewers, the difference was far more pronounced in patients with squamous cell NSCLC histology (41% vs. 25%), while there wasn’t any real difference between the Abraxane and taxol arms for adenocarcinoma histology (26% vs. 25%). Interestingly, the investigators themselves had the same RR assessment of 37% vs. 30% for both major NSCLC histologic subtypes:

abraxane-rr-by-histology

In terms of side effects, Abraxane was associated with less severe sensory neuropathy and less neutropenia (low white blood cell count associated with higher risk of infection) but higher rates of anemia and thrombocytopenia (low platelet counts).

Abraxis, the company that makes and markets Abraxane (it’s FDA-approved for breast cancer already) is expected to seek an indication in lung cancer based on these data. As I had indicated in my post about the press release back in March, the data at ASCO were received with a sense that response rate data don’t provide the most compelling overall picture in the absence of any evidence that patients remained without progression and/or lived longer for getting Abraxane, and I would say that the overall tone of the audience was critical of RR as a primary endpoint and the basis of any meaningful conclusions.

So what can we say? I’d really be far more swayed by data showing a significant improvement in the endpoints that I think translate more directly to real clinical benefits for patients (I think my patients would rather have minor tumor shrinkage that lasts a year or more, vs. more significant but also more transient tumor shrinkage, and they’d especially prefer to have their treatments extend their survival significantly), but I’m impressed that a difference in RR in the 7% range is at least worthy of our attention. I’m actually far more impressed in the difference of 16% in patients with squamous NSCLC, if that’s real — not only is that a pretty compelling difference, but it’s in a patient population for whom new treatments with meaningful benefits have been maddeningly hard to come by. If we could find a particular chemo agent that is especially effective in squamous cell histology, that would be very encouraging.

The response rate data give only a preliminary glance at the whole picture, but I’m hopeful that this may represent a meaningful incremental benefit for NSCLC patients with squamous histology.


3 Responses to Positive trial for Abraxane in NSCLC: Follow-up From ASCO

  • catdander says:

    Thanks Dr. West.
    Is there a simple explanation for the differences in findings between the investigators and the independents?
    and
    How long before information is available about PFS and OS is available? or at least that can compare to taxol.
    and
    Do you think some onc will now consider giving abraxane alone to a patient with squamous nsclc who has responded well to previous lines of treatment that didn’t include a taxane.
    thank you again,
    catdander

  • gberazadi says:

    Last year I was in a trial of Carboplatin plus Abraxane. First month scan was good but second month did not feel well, had to postpone treatments because of low blood counts and progression. This is the first time that I lost my hair and had to interrupt chemo. We followed 1 month with Alimta, very easy and got reducctions and stability. After many months without chemo, not aproved for maintenance in Canada, cancer progressed and I am on second month of Tarceva. I am 72, male, diagnoses 5 year ago NSCLC adenocarcinoma Stage 2. Did 1 month Iressa, had 1 lobe removed, Cisplatin + Vinorelbine, after 2 years mets in 2nd lobe and maybe rib, did Radiation, tumors in both lungs now, Carboplatin + Abraxane, Alimta, Tarceva. Not bad 5 years, enjoy almost a normal life, traveled a lot, and gainned weight! Problems neuropathy, fatigue, arm pain, leg cramps. If Tarceva fails as non smoker my hope is Crizotinib 1066 but ALK mutations are in under 10% of population and not available in Canada yet to be tested. Carpe Diem.
    Grace is amazing. Thanks, Guillermo

  • Dr West says:

    There’s no detailed assessment of that. The investigators can argue that they have more context to interpret what perhaps will be ambiguous imaging findings. On the other hand, they (we) may also be more biased to interpret results as favorable because they want their patients to be doing well; they may also allow their clinical perception of how a patient is doing to affect their judgment of the findings on the scans. It’s not completely clear who’s more right or wrong, but we generally rely on the professional radiologists who comprise the independent reviewing committee as being more objective.

    The company suggested that additional efficacy data would be available later this year. I’ll admit that it makes me skeptical when a company has response rate data in March but doesn’t have progression-free survival data, at least. There isn’t that long of a lag between the first few scans and a detection of progression in many patients (unfortunately). Since we generally see that companies will shout any positive results from the hill tops as early as possible, I always wonder if less than positive results are more subject to being sat on for a while. I’ll be pleasantly surprised if other efficacy measures fall significantly in favor of Abraxane.

    I’m pretty sure some oncs will be inclined to do all sorts of things, and I think it’s a reasonable thought to pursue Abraxane in NSCLC, particularly for squamous histology. Response rate isn’t among the more compelling endpoints in my mind, but it’s something, and if other endpoints fall in favor of Abraxane, I think it will emerge as an increasingly used option. And of course, if the FDA approves it in lung cancer, that’ll have a huge impact. Right now, as a fairly expensive medication that doesn’t have an approval in lung cancer, many oncologists may be reluctant to administer it and then find that it won’t be covered by a patient’s insurance company.

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