Iressa GEFTINAT - 1250015

Hello waterspring
I'm so sorry the prices of drugs are keeping your father from getting what he needs. It's a horrible growing problem. We won't be able to comment on whether the two drugs will have the same effacacy. But I will ask our Parmacology doctor to chime in.

All the best
Janine
Forum moderator

Waterspring, this is a tough question to answer. In the United States, we only have one supplier of the drug (actually for gefitinib, we don't even have one for regular clinical use since we use erlotinib/Tarceva instead). This is due to the brand/generic laws in the United States that are different in other countries.

In general, a generic form of a drug (like gefitinib) has to demonstrate the same properties of the brand name (Iressa) in terms of how it behaves in the body and what it is composed of before it gets approved. I do not know any specific information about the products you have listed but I would believe them to behave the same in the body. Generally efficacy studies on the generics are not done so we assume if the drug behaves the same in the body as the brand name, they will have the same effects.

Since there is a large international following on this site, perhaps another patient has had experience with the specific generic product you are considering.

Best wishes,
Dr. Walko

Waterspring, sorry to hear about your father, and about the high price of Iressa.
(Just as background for everyone - there have been protracted legal battles in India with drug companies trying to defend their patented cancer drugs against cheaper generic versions. For example earlier this year a company called Cipla began marketing cheaper versions of Nexavar and Temodar.)

I agree with Dr Walko that it would be really useful to hear from anyone who has had experience with these generic alternatives - we've had similar questions from India about cheaper alternative versions of Tarceva.
Waterspring, Is it worth contacting AstraZeneca, explaining your father's situation and asking if they can help in any way with the cost of the Iressa? They may say no, but it is worth a try. Best of luck.

How is it possible to obrain Iressa in the US? My mom tried Tarceva but it didn;t work for her, even though she had the EGFR mutation. It could be possible that maybe Iressa might work for her.

Needinfo, I think we might need some info on you! I don't see a forum signature, and it's important for the doctors to know that your mother has the EGFR mutation in exon 20 and exon 21, as described in one of your previous threads:
http://cancergrace.org/topic/tarceva-did-not-work-need-help
My understanding from Dr West's comments in that thread is it's hard to predict how such patients will respond to different treatments, but I can't see why Iressa would be helpful if Tarceva wasn't. Hope your mother is doing well.

Iressa isn't FDA approved, any longer, so can't be obtained in the US. Like certain spring said it isn't shown to have different efficacy on people who are EGFR positive. Afatinib may be an option.

Here is the latest info on resistance to tarceva there are further reading links at the end. Which from what I understand you move right to in you situation.
http://cancergrace.org/lung/2013/02/23/riely-on-targrx-acquired-res/

I don't think this is a regular case of Tarceva resistance. From what I understand, Needinfo's mother was only on Tarceva for a month when it became clear that it wasn't working, perhaps as a result of her conflicting exon 20 and exon 21 combination. I think she's been on chemo as second-line? It would be really useful to have a forum signature giving her history, to avoid confusion. A new thread might be appropriate as well - this isn't really about Geftinat, which is an interesting topic in its own right.

Thanks cs, and good suggestions for needinfo too. That way we can get doctors the appropriate authorities involved.

This is what I thought might apply, http://cancergrace.org/lung/2013/02/22/inherited-t790m-mutation-oxnard/

she is going well on alimta and carboplatin right now....really hoping that afatinib works too eventually, any idea when it might get approved? giving Iressa a shot would of been nice...yes, definitely need to do a signature line...thanks!

I think it would be exceptionally unlikely, bordering on unprecedented, to have someone with an EGFR mutation who didn't respond to Tarceva (erlotinib) demonstrate a more favorable response to Iressa (gefitinib). They have essentially the exact same mechanism of action, and the evidence in EGFR mutation positive patients is that they work remarkably similarly, though the standard daily dosing of Tarceva at 150 mg daily provides a stronger total dosing than Iressa at its standard daily dose of 250 mg daily (Tarceva 150 mg daily is about equal to Iressa 700 mg daily in lab-based studies). Accordingly, though we haven't had Iressa in the US since about 2004, I haven't had a flickering thought that it would be valuable to have again except as a cost competitor for Tarceva, since they really seem to work comparably well in EGFR mutation-positive patients.

I think the projection is something like mid-year or Q3 for afatinib approval. However, while there's some reason to think that afatinib might possibly be more effective than Tarceva or Iressa in EGFR mutation-positive patients, there's really no compelling evidence of that right now, and I must confess that I'm skeptical it will be more of anything other than more challenging for side effects than Tarceva or Iressa in EGFR mutation-positive patients.

Good luck. It's great that she's doing well on standard chemotherapy at this point.

-Dr. West

Just to emphasise again that Needinfo's mother has the exon 20 mutation as well as exon 21. I think Dr West was unaware of this when he answered the question. This is why it's so important that people do a forum signature giving relevant history.
Needinfo, it sounds to me as if your mother's exon 20 mutation has trumped or triumphed over her activating exon 21 mutation. It's hard otherwise to explain her lack of response to Tarceva. Can you take her to a specialist, as Jazz suggested in your earlier thread? She may have other mutations that might make her suitable for a clinical trial. Dr West in this post highlighted the work of Dr Geoff Oxnard, who is in Boston:
http://cancergrace.org/lung/tag/exon-20-2/
http://www.ncbi.nlm.nih.gov/pubmed/23328547

I actually don't think that would change my answer at all. Right now we don't have much data on exon 20 mutations in general, and we certainly don't have any evidence that one EGFR inhibitor works better than another. So my sense remains that there isn't a clear reason to anticipate that one EGFR inhibitor would be far superior to another. Possible? Yes, but I think unlikely, and I think a different avenue of treatment would be more likely to be fruitful.

-Dr. West

needinfo,

1. FYI, I know of a US citizen who has learned of some promising experimental research for their lymphoma or leukemia that uses Iressa (yet Tarceva doesn't work for that). Upon exploring the research they found they might be able to get the drug at the Canadian clinical trial site, but of course that would involve frequent trips to Canada. I'm not suggesting at all that it would be useful for you to try it, but just mentioning how some USA residents might get it outside the country if there were a reliable reason.

. . .

2. An old chart I have that uses data from "Sharma et al Nature Rev Cancer 7, 169, 2007" suggests that most Exon 20 mutations are resistant to 1st generation inhibitors, with only a couple of specific exceptions that are sensitive (V765A, T783A). T790M is the most common variant of Exon 20 mutation, and as you say in the URL link someone else provided there is research going on into the possibility of an inherited T790M in some families. You might be able to get free testing to see if you (and maybe your family members?) had an inherited T790M long before you ever developed lung cancer. That video doesn't make it easy to find out where to find out the details for that, so here is a link for your convenience:
http://www.dana-farber.org/Adult-Care/Treatment-and-Support/Treatment-C…

In contrast, all the Exon 21 variants identified in that old data were sensitive.

So maybe you have a pair of variants, one probably responsive to Tarceva and one probably unaffected by Tarceva? If that is the situation and these are in different cancer cells, then maybe Tarceva could suppress some of the cells but not the other. I'm not sure if it's possible for both to be present together in the same cells, but if so then I wonder if maybe the drug wouldn't stop any cells (though maybe it could slow them a little). Your scans might have indicated whether there were any specific areas of benefit during that month.

Depending on what specific variants of EGFR you have, a 3rd generation experimental drug or combo (in clinical trial) might be worth discussing with your oncologist. E.g., afatinib + cetuximab, if tolerable and not closed to new participants. Or consider treatment options that don't care about EGFR status.

. . .

3. BTW, another thing to consider is that a portion of people with Asian ancestry inherit a BIM gene that can make Tarceva ineffective. (I don't think BIM is found in caucasians.) If you have an EGFR variant that doesn't respond to Tarceva or Iressa anyway, then this probably wouldn't matter, but if you are Asian then your oncologist might want to know your BIM status and consider that in your treatment options, too. (E.g., an experimental clinical trial that tries to address both BIM and EGFR.)

Although these ideas probably aren't helpful to you, I thought I'd throw them out here just in case you wanted to understand more about factors involved.

Best hopes,

Craig

P.S. -- I'm just another patient, not a medical professional. Ask your oncologists for details. (But ask me if you need some research citation reference for something I said.)

Hello all.

My sister needs Iressa for NSCLC. Iressa is available in my country, but it is very very costly.

Just like waterspring posted about 2 years ago (see above), I am looking to getting gefitinib from India, and I would like to know whether other readers in this forum, in the meantime have had experience with this drug or can point me to another forum where I can find the answer.

Thank you for your attention

I am not familiar enough with details of this agent to say that it is really interchangeable or not with gefitinib as manufactured by AstraZeneca. I believe it is quite similar but cannot attest to it having identical efficacy.

Good luck.

-Dr. West

My understanding is that generic gefitinib (eg geftinat) is manufactured by companies like NATCO in India. It is still somewhat expensive with prices up to 300 USD per month, depending on the country. It seems like it can be ordered online. This link is one example.
http://www.cancercarepharmacy.net/geftinat-250-gefitinib-250/4.html
If someone simply cannot afford Iressa, Tarceva, Conmana, etc then it seems like it could be a reasonable option in that setting.

Waterspring, a couple things: People are saying that because gefitinib and erlotinib have the same mechanism of action, the efficacy should be the same. That is false. All of these drugs are different, despite the same mechanism. They may act differently in different patient types. We saw "super-responders" to gefitinib. Also, female, Asian, non-smokers did best of all groups in various trials. So, take that off the table. Next, have you tried to contact AstraZeneca to ask about their "Patient Assistance Program?" If your father truly cannot afford IRESSA, AstraZeneca may be able to help with their PAP. Finally, since these drugs are not biologics, they only require that the generic be proven to be "bioequivalent," and; therefore, therapeutically equivalent. Natco is a very reputable company and has shown a unique ability to make generic forms of very difficult to manufacture drugs, like COPAXONE. Therefore, I would say that if Natco's version of IRESSA is an approved generic in India, you can expect the same results that you would see with IRESSA. People will try to tell you that generics are allowed to have a fairly large variance vs the brand. What they don't tell you is that "variance" is the EXACT same variance that they allow brands to have between different batches of the same drug, when being manufactured. I hope this helps!