Afatinib Approved by FDA - 1257876

That's a great news. At least from my husband's experience, it is better than Tarceva, although the side effects is hard to handle.

After it being approved by FDA, could doctor comment what are the impacts on the patients who are using it now either through clinical trials or compassionate program?

Do patients need to switch to buy the medicine or continue on compassionate/clinical trial program? Thx.

Great news!

I must confess that my review of the data and personal experience suggest that in the vast majority of patients, afatinib is just a considerably more toxic version of Tarceva (erlotinib). There isn't an iota of a scintilla of evidence that afatinib is more effective than either Iressa (gefitinib) or Tarceva for first line therapy in EGFR mutation positive patients who are about to start first line therapy. -- the evidence we have is that afatinib provides a better progression-free survival and response rate than chemo for EGFR mutation-positive patients in the first line setting; this is exactly what we've already seen from Iressa and Tarceva. Afatinib, however, leads to considerably more rash and diarrhea, so I am completely unenthusiastic about using it over Tarceva, which is challenging enough.

As for using it in EGFR mutation-positive patients with acquired resistance, the data included in the press release is the definition of damning with faint praise. The response rate was under 10% in the best data they could dredge up in the world, and other experiences have been less favorable than not. There are no doubt rare patients who may benefit from it more than other EGFR TKIs, but every patient I've ever treated with afatinib after progressing on Tarceva has only experienced progression at the earliest scan afterward, along with greater toxicity than they ever had with Tarceva. Also, trials that have looked at Tarceva after Iressa or even progression after prior Tarceva and an interval off of it have experienced response rates comparable to what you see with afatinib.

So while I agree it's an option to consider, I think it's incorrect to infer or to believe any claims that it's anything more than another EGFR TKI with comparable activity and greater toxicity than other options, except perhaps in very occasional patients.

I'm sorry to be so underwhelmed, but that's my honest view. New isn't necessarily improved.

-Dr. West

How do the three drugs compare in terms of price and availability? I don't understand why the FDA thinks we would need 3 drugs doing essentially the same thing. It's confusing enough for patients as it is. So I can understand why it might be approved if it provides a much cheaper or widely available alternative to Tarceva and Iressa, but otherwise, why bother?
Debra

It was approved because afatanib trials were designed in a way that they formally tested afatinib as first line treatment vs. chemo in EGFR mutation-positive patients in a trial conducted internationally, including US-based patients (few from the US, actually). Tarceva was approved based on the EURTAC trial, a European trial of Tarceva vs. chemo in EGFR mutation-positive patients, and I think it was unclear that it would be approved for first line based on an exclusively European trial. As it was, the FDA essentially approved two drugs for the same indication concurrently, but as I said above, it's not clear to me that afatinib offers any benefit over Tarceva in this setting.

-Dr. West

Yan,
I believe one can remain on the clinical trial to receive Afatinib until the end date or progression. I'm not sure about compassionate use, how that works once the drug is approved.

I would agree with Dr. West as regards 1st-line use of Afatinib, IMHO. I suppose if Tarceva or Iressa doesn't work for some reason, it's good to have Afatinib, which is slightly different. As for post-Tarceva progression, I do believe the Afatinib-cetuximab combination is far more effective than Afatinib alone, but I represent a small percentage of patients probably. I can't downplay the year of life it gave me, of course.

The side effects were terrible, compared to Tarceva, which I'm on again and seems like a cakewalk. That said, I guess it's good to have a back-up... But it is surprising, the 1st-line indication. I'm wondering what the projected commercial price is?

My perspective is that I'd distinguish my more pessimistic comments above from my perspective on the afatinib and cetuximab combination, which I think there's more reason to be hopeful about. However, that work is still very early, and the side effect profile remains a very real concern as well think about broadening our experience with this regimen to a population of patients that don't necessarily have the health, motivation, or resources to travel to the few sites offering the phase I/II trials. I look forward to seeing more research with this combination, but between now and then, I suspect it may be an uphill battle to get insurers to pay for cetuximab (and perhaps afatinib) outside of their approved settings, given their cost.

As for afatinib on the compassionate use protocol, the expectation is that people on it will need to transition to commercial drug once it becomes available (it is often 1-2 months between FDA approval and commercial drug actually becoming available to patients).

-Dr. West

I haven't learned anything else about sorafenib trials for acquired resistance -- I don't think that anything is moving forward right now.

I think your assessment is good of the toxicity vs. potential benefit of switching to afatinib from Tarceva based on slight progression. I don't know the pricing of afatinib yet, and I hope you're right, but I think that the prices of new agents seems to only rise. I don't think the price of Tarceva will be heading down, though years ago I did write a post saying that if there was any good reason to bring Iressa back to the US market for patients with an EGFR mutation, it would be to add some competition and no longer give Tarceva a monopoly for the patients who really benefit greatly from it.

-Dr. West