exon 20 insertion mutation

Portal Forums Lung/Thoracic Cancer NSCLC Stage IV NSCLC exon 20 insertion mutation

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April 30, 2018 at 1:37 pm  #1294328    

sch1979

Hi. My father was diagnosed with stage iv lung cancer two weeks ago. It has spread to his bones and adrenal gland. Today we found out that he does not have any targetable mutations. Can anyone advise as to what treatment he is likely to receive and the prognosis? We are getting a second opinion at Sloan Kettering tomorrow, but are anxious to know what this all means. We were told that it hopefully would have a targetable mutation, so we are devastated.

April 30, 2018 at 2:56 pm  #1294329    

onthemark

It’s good you are going for expert advise at Sloan Kettering. Most lung cancer patients, unfortunately, do not have a targetable mutation but there have been advances with immunotherapy.

The FDA recently granted priority review of pembrolizumab (Keytruda) for use in combination with pemetrexed and platinum chemotherapy for the treatment of patients with newly diagnosed metastatic nonsquamous NSCLC. If you have adenocarcinoma then this would be worth discussing tomorrow.

The prognosis with this triplet combination depends to some extent on expression of PD-L1 but it works for all expression levels.

At a median of 10.5 months follow-up, pembrolizumab plus chemotherapy resulted in significant improvements in both PFS and OS compared to chemotherapy alone. The estimated 12-month OS rate was 69.2% with the pembrolizumab combination, compared to 49.4% for chemotherapy alone (HR 0.49, P<.001). The median OS was not yet reached in the pembrolizumab combination group, and was 11.4 months in the placebo combination group. The OS benefit with pembrolizumab was consistent across all prespecified patient subgroups, including PD-L1 expression (PD-L1 <1%: HR 0.59). The addition of pembrolizumab resulted in a 3.9-month improvement in PFS (8.8 months vs 4.9 months; HR 0.52, P<.001). Overall response rate (ORR) was 47.6% in patients receiving the pembrolizumab combination versus 18.9% in patients receiving the placebo combination (P<.001).

“Placebo combination” in this quote means that the patient received the same two chemotherapy drugs but a placebo was substituted for Keytruda to make this double blind.

http://www.primeoncology.org/primelines/pembrolizumab-chemotherapy-combination-for-nsclc/


10/2015 Chest xray found a nodule as part of a physical (no symptoms).
01/2016 Upper left lobe lingula preserving lobectomy stage 2b for 1.9 cm invasive adenocarcinoma with additional 2 mm AIS nodule found in pathology.
03-05/2016 Sixteen weeks of adjuvant cisplatin/vinorelbine.
07/2016 Durvalumab adjuvant clinical trial discontinued after 1st dose knocked out thyroid.
12/2016 Revised to stage 1b (due to VPI) after new guidelines for multifocal lepidic lung cancer.
07/2019 Next scan.

  • This reply was modified 3 months, 2 weeks ago by  onthemark.
  • This reply was modified 3 months, 2 weeks ago by  onthemark.
April 30, 2018 at 3:03 pm  #1294331    

scohn

Hi sch1979. I am so sorry to hear about your father’s diagnosis. My wife was diagnosed 3 years ago with stage IV NSCLC, with bone metastases, but I still remember vividly those first days/weeks, and all the emotions they contained – my frantic desire to find out everything at once and do something immediately. I also remember when the main targetable mutations came back negative.

I also know how helpful this site has been for me. I am sure the moderators will answer your question, but I just wanted to give you a few thoughts from our story, and to let you know you aren’t alone.

My wife has HER2 exon 20 insertion (I assume from the title of your post that your father as an EGFR Exon 20 insertion?). For HER2 there are some drugs (like afatanib) with some effect, but our oncologists said it doesn’t work well. But, I guess my story is that my wife has been treated with 2 conventional chemotherapies, and 1 clinical trial, which all have worked well for a time. She was on carboplatin/alimta for several rounds, then later on a clinical trial that worked for about 1.5 years, followed by another conventional chemotherapy that has been working for about 6 months. So I just want to let you know that sometimes conventional therapies also do great! But we have come to realize that in many respects what they told us at first seems to be true. Each patient/cancer pair is kind of unique and requires its own set of treatment determinations. I am sure the people at Sloan Kettering will help you think about the best current standard treatments in your father’s case.

I also want to let you know that if it is an Exon 20 mutation, there is a new clinical trial you may want to discuss with the oncologists. It is testing a new drug designed specifically for Exon 20 mutations (for both EGFR and HER2), and you can find it here: https://clinicaltrials.gov/ct2/show/NCT02716116.

I’ll be thinking of you & your father, and may your meeting at Sloan Kettering go well!
Regards, scohn


Wife, lifelong non-smoker, dx 4/24/15 adeno NSCLC stage IV-2 bone mets, 1 lymph node. HER2 Exon 20 mutation. 6x Carbo/Alimta – >50% reduction in primary tumor, lymph nodes, & bone. Alimta maint. not effective -growth & new liver mets. 11/15 – Opdivo; Not effective-add’l growth. 4/16 – PF-7020- large reduction of tumor and mets. 11/16-mixed results, liver mets stable. 2/17-All Stable. 8/17- Add’l growth-off Pfizer trial, 9/17 Gemzar- reduction then stable. 8/18 – Mixed results – new treatment?

April 30, 2018 at 3:16 pm  #1294332    

sch1979

Thank you so much for your responses. This has been quite a journey already.

Yes, it is an EGFR mutation. I cannot tell from the test results if there is a PD-L1 expression. I don’t see that stated anywhere on this piece of paper (so much medical jargon to learn). I’ve heard from several folks that everyone responds differently and while that is reassuring (given the “statistics”), it also leaves us without certainty. But I guess that is the new normal now. We have to take it one day at a time, I suppose.

The test results show it is p.ser768_Asp770dup mutation. I’m not sure what that means, but just in case it means something to you, I am adding it here. It also says it is mutation negative for AKT1, ALK, BRAF, DDR2, EPHA2, ERBB@, FGFR1, FGFR2, FGFR3. KRAS, MAP2K1, MET, NRAS, PIK3CA, RET, ROS1, TP53.

Again, thank you for the responses. SCohn, has your wife returned to work? When treatments “work,” does that mean that the patient feels good, or should we expect a bad quality of life for as long as he makes it?

April 30, 2018 at 4:19 pm  #1294335    

scohn

Hi sch1979.
Again, each person is different, but my wife has done well overall – the tumor is now stable, and her energy and mood are really good. She is actually retired now, and I will be retired in a little over a year! We have made a number of trips since her diagnosis, and, as before the diagnosis, she seems to perpetually have more energy than me! She currently volunteers twice a week to teach English for adult ESL students.

You can search in GRACE for descriptions of our journey so far, but basically the types of side effects have varied dramatically between each kind of treatment. In our case my wife has had very little effect from the cancer itself, and has spent much more time managing the medication side effects. If you are ever interested I can tell you more about her side-effect management than you would ever want to know.

But, to your general question, we have been blessed that the treatments have kept the cancer at bay, and has allowed my wife a very good quality of life! We have traveled to Israel, Canada, California, and the Galapagos, and even organized my daughter’s wedding since her treatments started. My guess is that the clinical trial drug she was on had almost as few side effects as any of the targeted drugs would have had. For a time she even returned to her volunteering as an AYSO soccer ref. And her current treatment (Gemzar) seems to be effective (keeping tumors small and stable – down but not out) with relatively few side effects (once she had a port put in – Gemzar treatment can be pretty caustic going in). So, each day a quick donning of a scarf, hat, cap, or beret for the previous hair loss and off she goes!

And I know what you mean by lack of certainty. We have tried to learn to take each treatment, and each CT scan one at a time, since we never know how long these treatments will last. But, as onthemark said, there are lots of treatment regimens being tested and developed.

Best wishes again for a productive SK consult.


Wife, lifelong non-smoker, dx 4/24/15 adeno NSCLC stage IV-2 bone mets, 1 lymph node. HER2 Exon 20 mutation. 6x Carbo/Alimta – >50% reduction in primary tumor, lymph nodes, & bone. Alimta maint. not effective -growth & new liver mets. 11/15 – Opdivo; Not effective-add’l growth. 4/16 – PF-7020- large reduction of tumor and mets. 11/16-mixed results, liver mets stable. 2/17-All Stable. 8/17- Add’l growth-off Pfizer trial, 9/17 Gemzar- reduction then stable. 8/18 – Mixed results – new treatment?

April 30, 2018 at 4:36 pm  #1294338    
catdander forum moderator
catdander forum moderator

Hi sch1979,

Welcome to Grace. I’m so sorry to hear about your dad’s diagnosis. The jargon will become common place in time. Onthemark and Scohn have given you some good ideas on what you may expect from your appointment at SK. The PD-L1 test may not have been given. Testing is still somewhat non standard since the playing field of targetable agents being tested is expanding and contracting so quickly. You’ll want to get input at SK about immunotherapy combos and promising trial options for insertion exon 20.

I look forward to hearing about your dad’s appointment and I’m sure he’ll be closer to making treatment decisions soon.

All best,
Janine

April 30, 2018 at 5:11 pm  #1294340    

onthemark

Following up on everyone’s comments, I’d also ask about poziotinib for exon 20 NSCLC.

“A drug that failed to effectively strike larger targets in lung cancer hits a bulls-eye on the smaller target presented by a previously untreatable form of the disease.”

we’re encouraged by early clinical trial results that show 7 of 11 patients (64 percent) with EGFR exon 20 mutations have confirmed tumor shrinkage after poziotinib treatment,” says John Heymach, M.D., professor and chair of Thoracic/Head and Neck Medical Oncology. “We need to see if these unprecedented response rates are maintained through the remainder of the trial, but our scientific findings provide a basis for optimism.”

So far, 47 patients have enrolled in MD Anderson’s original phase II trial for EGFR and 12 are enrolled in the HER2 arm. The drug’s owner, Spectrum Pharmaceuticals, has opened a multi-center phase II trial.

https://www.sciencedaily.com/releases/2018/04/180423125207.htm


10/2015 Chest xray found a nodule as part of a physical (no symptoms).
01/2016 Upper left lobe lingula preserving lobectomy stage 2b for 1.9 cm invasive adenocarcinoma with additional 2 mm AIS nodule found in pathology.
03-05/2016 Sixteen weeks of adjuvant cisplatin/vinorelbine.
07/2016 Durvalumab adjuvant clinical trial discontinued after 1st dose knocked out thyroid.
12/2016 Revised to stage 1b (due to VPI) after new guidelines for multifocal lepidic lung cancer.
07/2019 Next scan.

  • This reply was modified 3 months, 2 weeks ago by  onthemark.
  • This reply was modified 3 months, 2 weeks ago by  onthemark.
May 3, 2018 at 8:45 pm  #1294371    

sch1979

We found out today that the pd-l1 was 60% which apparently is rare for an exon 29 insertion, but it means immunotherapy is an option. The treatment plan right now is keytruda, carboplatin, pemetrexed. Has anyone had this combination?

May 4, 2018 at 5:29 am  #1294374    
JimC Forum Moderator
JimC Forum Moderator

You can see my response in your other thread at http://cancergrace.org/topic/keytruda-carboplatin-pemetrexed-combo#post-1294373

JimC
Forum moderator


Jul 2008 Wife Liz (51/never smoker) Dx Stage IV NSCLC EGFR exon 19
4 cycles Carbo/alimta, 65% shrinkage
Tarceva maintenance
Mar 2010 progression, added Alimta, stable
Sep 2010 multiple brain mets, WBR
Oct 2010 large pericardial effusion, tamponade
Jan 2011 progression, start abraxane
Jun 2011-New liver, brain mets, add Tarceva
Oct 2011-Dx Leptomeningeal carcinomatosis; pulsed Tarceva
At rest Nov 4 2011
Since then: http://cancergrace.org/blog/jim-and-lisa

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