Best next step for HER2 mut.+. met.NSCLC after progression on Herceptin?

Portal Forums Cancer Basics Clinical Trials and Drug Development Best next step for HER2 mut.+. met.NSCLC after progression on Herceptin?

This topic contains 3 replies, has 3 voices, and was last updated by  safille 1 year, 4 months ago.

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March 5, 2013 at 12:57 pm  #1254492    

safille

Dear Drs. all (and Janine, thank you for your past response!),

I had a very helpful response from Dr. Pinder on bone mets (many to areas of the spine/pelvic/iliac area, incl. some muscle and joint), in my father’s case–73-yr old with metastastic NSCLC (BAC/mixed adeno), with HER mutation. Bone mets aside (if, Lord willing, that is possible!) we need to also determine next steps in a way-more-than-multi-line history. Afatinib was the most successful (2010-11), which was followed by Herceptin/Taxol (2012-present), with most of the mets. in the spine/pelvis. He is in France, and I’m following trial possibilities, but would be very grateful for any preference you might have for top options as I see them:

*if approved for compass. usage: Afatinib or dacomitinib (assuming retreatment may have a response)

*PD-1 or PD-L1 trial if one opens (MPDL3280A is a possibility)

*if possible (big if): combining Cetuximab with Afatinib, given the good results in the EFGR-mut. trial:could these carry over to HER2 acq. resistance?

*retry Alimta, on which progress. was slow?

*AUY922 trial (HSP-90 inhibitor)?

Thank you for any insights. I realize we are way out in uncharted territory here, and there are no golden answers, but I would be very grateful for any thoughts on leanings you might have one way or another.

Case:
2005-06 after surgery, Cisplatin plus vinorelbine (progr. quickly)
2006 mets to other lobes: Tarceva (progressed), Avastin
2007-2009 Alimta, Avastin, progressed.
2009 Surgery at Mayo for large bone met at L1-L2
2009-2010 Gemcitabine; progressed quickly
2010-2011 LUX;LUNG‚Äď15% response with Afatanib, eventually progressed in 2012
2012 feb. vertebroplasty
2012 spring-now Herceptin/Taxol; significant progr. esp. to bone

March 5, 2013 at 1:45 pm  #1254494    

catdander forum moderator

Hi safille, I will ask a doctor to respond. Leanings towards one or another are way out of my league for comment.

Except, ;) to say it looks like your dad was on alimta for a long time with slow progression and several years ago. I assume it’s readily available and it has a low toxicity profile (some say less than tarceva alone in some instances).

If PD 1 is an option it’s an option now and may not be later. Alimta will always be there.

Cetuximab with Afatinib was a very tough combo and sometimes just afatinib alone for some. I’m not sure the combo is even available.

You may be familiar with these, http://cancergrace.org/topic/afatinib-cetuximab-trial-user-group

http://cancergrace.org/lung/2012/09/12/neal-lux-lung-3/

And from the most recent conference on targeted therapies last week Dr. West and Mark have put together the lengthy list of shorts. http://cancergrace.org/general/2013/02/20/iaslc-vids/

Janine


My husband, 53 @ dx of stage 3 squam nsclc R. pancoast tumor 8/09 caused destruction of 3 ribs, touching brachial plexus. 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable). Chemorads, 9/09. MRI by pancoast specialty surgeon 11/09 spine met found, stage IV, Rad to spine, Chemo changed from cis/etop to navelbine/carbo. 6 cycles total. Tarceva 2/10-11/10. 3cm tumor L lung, biopsy undx w/collapsed lung. Gemzar, 12/10 through 7/12. NED 3/12, stop tx 7/12. Remains NED as of 2/14.

March 5, 2013 at 2:15 pm  #1254495    

Dr Spigel

The thought on returning to Alimta is a good one – considering there was a prolonged benefit and it’s been over 3 years since then.

Ideally a clinical trial is the next best step – antiPD1/PDL1, an antibody-drug conjugate, or HSP90 inhibitor-bsed combination are all reasonable next steps. If available, I’d sequence beyond EGFR and HER2 – looking for another potential target – assuming that there are phase I trial opportunities he could pursue. If not, then Alimta is a very reasonable next step.


David Spigel, MD
Thoracic Oncologist and Director of Clinical Research

Views expressed here represent my opinion, not those of GRACE or Sarah Cannon Cancer Center. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

March 7, 2013 at 6:14 pm  #1254539    

safille

Thanks very much for the answers–sorry, snow day & kiddos at home for fun delayed my response :) ! those are helpful to factor in & I think we will explore the trials options. In my dad’s case afatanib was in fact very tolerable, but he has never tried cetuximab; Alimta (which he took with Avastin) was quite tolerable as well. In both cases the mets were primarily to the spine, not so much spreading further in the lungs. thanks again for your input. Best,
Laura

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