What next? Afatinib, Chemo? - 1253823

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godad
What next? Afatinib, Chemo? - 1253823

My father was diagnosed with stage IV EGFR+ (L858R) NSCLC in May of 2011. Started on Tarceva, after minor progression in liver after about 4 months moved to carboplatin/paclitaxel + bevacizumab for 6 cycles with good response. Moved to maintenance with pemetrexed and bevacizumab until the last scan showed progression in bones, lungs, and especially significant progress in the liver. At this point we are struggling with what to do next. We are in the SF Bay Area and have access to Afatinib through expanded access (although I'm not sure if that rules out adding cetuximab), but we are somewhat skeptical about that option given the relatively short response on Tarceva and the fact that he progressed in the liver the last time, which is where we are most concerned now. Oncologist is recommending gemcitabine and cetuximab, which is not a combination that I have heard of in lung cancer. At Kaiser so phase 1 trials are out of the question. What gives us the best chance (EGFR inhibitor or chemo) for a response at this point? If chemo, is this combination reasonable? Dad seems to physically be ok.

catdander
Reply To: What next? Afatinib, Chemo?

Hello, I'm very sorry your dad has progressed. Though it's always a good sign that he seems to be physically ok.
Although on the outside it appears you're asking a pretty simple question but in truth it's pretty complicated and depends on his individual case.

I will paste links to some of the most recent thoughts on treatment as well as ask a doctor to comment on them. You should hear back within the day from the doctor and I'll add links to a following post asap.

I wonder how slight the progression on tarceva was. Often people with an egfr mutation will wait give a little more time to tarceva when progression is small.

Doctors have seen afitinib work well when tarceva didn't.

Your dad is at a stage in his treatment where he has many options for trials. A second opinion is helpful for many reasons one being being seen by a specialist will have up to date info on trials in the area that may fit his profile.

All best,
Janine
forum moderator

godad
Reply To: What next? Afatinib, Chemo?

Thanks for the quick response! We are currently seeking a second opinion, as we do understand that it is a complicated question.

During the initial Tarceva treatment, the progression was very minor. We were monitoring multiple legions, all of which were stable or continuing to respond, but there was 1 small new one that appeared in the liver. I will need to check my notes, but I believe it was only a few millimeters. We would have probably kept him on the Tarceva if we knew then what we know now. I think we are pretty hopeful that another try at an EGFR inhibitor will be effective, but given the fact that the liver seemed to be the area of initial resistance and now shows the most progression, we are not sure.

catdander
Reply To: What next? Afatinib, Chemo?

these posts probably aren't going to be so helpful but I'll post what I've got just in case you or others can use them, http://cancergrace.org/cancer-101/2011/11/13/an-insider’s-guide-to-the-second-opinion/

Standard for 2nd line, http://cancergrace.org/lung/2010/10/04/lung-cancer-faq-2nd-line-nsclc-op...

It sounds like you have a good understanding of what you're up against. I'll leave it to our doctors to discuss.
But I'm looking for a discussion on a possible reason for an egfr positive person not to do well on tarceva. It has to do, I think with an inherited gene mutation that most people acquire after a while on tarceva. I'll continue to look. If I've not made this up someone who knows more about will comment on it.

Dr West
Reply To: What next? Afatinib, Chemo?

As patients go through more and more treatments, the evidence-based options become more limited. Right now, Taxotere (docetaxel) is a treatment that he hasn't received and that has some established benefit for previously treated patients with advanced NSCLC. There's not really meaningful evidence about gemcitabine and cetuximab as a combination, but after several lines of therapy, there just aren't going to be evidence-based choices, so by necessity you're left being guided more by concepts and best judgment than hard evidence. Gemcitabine is certainly one of the agents that is among our more active against NSCLC and can be combined with cetuximab, which may or may not add any benefit here. There isn't very strong evidence that it improves outcomes, but the suggested treatment is certainly reasonable in a setting in which there isn't a clear best answer.

If you're interested in a second opinion in that region, Drs. Heather Wakelee and Joel Neal at Stanford, or Drs. Karen Kelly, Primo Lara, or David Gandara at UC Davis are some leading experts in that area who may have a trial option to suggest as well.

Good luck.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

drsequist
Reply To: What next? Afatinib, Chemo?

I agree with Dr. West that there is no standard option at this point and many chemo options are reasonable to think about, including docetaxel, vinorelbine or gemcitabine. An EGFR-directed trial would also be a good option, but you are right in that many of the tarceva-resistance trials are phase I and if he is a Kaiser patient, that may not be possible.

One innovative option outside a clinical trial is adding erlotinib to the chemotherapy. It can safely be given with each of the 3 chemo's listed above and there is retrospective data suggesting patients with EGFR mutations may do better with chemo + tarceva compared to chemo alone. This strategy is currently being tested in a prospective trial but many docs are already adopting theses combinations for EGFR mutation-positive trials.

In my personal practice, if no trial were possible I would probably give tarceva + gemcitabine as I have had some good experiences with that regimen.

Best of luck,

Dr. Lecia Sequist

godad
Reply To: What next? Afatinib, Chemo?

Thank you all for your input! I am happy to hear that my dad's oncologist's recommendation was reasonable, but would like to have as much information as possible before we make our decision. As far as the Afatinib option goes, am I correct in assuming that there is less excitement about its use as a single agent for someone who has progressed on Tarceva? We have confirmed its availability to us through the expanded access program but we don't think that allows us to add cetuximab to it (haven't confirmed yet).

Again, many thanks to everyone here at Cancer Grace. I have been following this site since my dad's diagnosis (despite being quiet on the message boards), and I can't say enough about what it has done to educate me and my family about treatment options and new research.

drsequist
Reply To: What next? Afatinib, Chemo?

I think afatinib would also be a reasonable thing to try. The expanded access program is for afatinib alone - you are right, there is no combination with cetuximab or with chemotherapy allowed. However, since it has been some time since he had an EGFR TKI, I think there is a decent chance of response to afatinib.

Best,
Dr. Sequist

godad
Reply To: What next? Afatinib, Chemo?

Thank you all so much for the input. We are hoping to get a second opinion soon, this will help us to frame our conversations.

catdander
Reply To: What next? Afatinib, Chemo?

That's great. Let us know how it goes.

Janine

godad
Reply To: What next? Afatinib, Chemo?

So just a brief update: We spoke with Dr. Neal at Stanford last week. My father actually has some history with him, as during his initial run with tarceva we combined it with hydroxychloroquine as part of a clinical trial he offered at the time. It was nice to see him again. After a lengthy discussion we decided on the gemcitabine + tarceva combo suggested by Dr. Sequist (and endorsed by Dr. Neal). The treatment starts tomorrow.

Thanks again to everyone for the input!

catdander
Reply To: What next? Afatinib, Chemo?

Godaddy go!
All the best of luck. I'll look forward to a good update soon.

Dr West
Reply To: What next? Afatinib, Chemo?

Great to hear. And Dr. Neal is an expert we know you can have confidence in.

Good luck.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education

laya d.
Reply To: What next? Afatinib, Chemo?

GOOOOD LUCKKKKK!

Laya