Priority Review Granted to Afatinib for EGFR+ Advanced NSCLC

Portal Forums Cancer Basics Clinical Trials and Drug Development Priority Review Granted to Afatinib for EGFR+ Advanced NSCLC

This topic contains 35 replies, has 11 voices, and was last updated by Dr West Dr West 2 years, 11 months ago.

Viewing 16 posts - 21 through 36 (of 36 total)
Author Posts   
Author Posts
January 21, 2013 at 2:11 pm  #1252866    
Dr West
Dr West

I agree that’s helpful. One of my questions is whether we might see people who don’t respond to one but do respond to another. I don’t know if he’s representative of a broader group, but it’s very interesting (and very good for him!) that afatinib did provide real incremental value. Knowing that there are a few more people like your husband could make a real believer out of me.

-Dr. West

January 22, 2013 at 10:46 am  #1252894    

certain spring

The trouble is, how many such people are there? I imagine most oncologists whose patients don’t have a good response to Tarceva are going to be looking for other treatments altogether, not other TKIs – though obviously it is great that Yan’s doctor thought of trying afatinib.
Dr West, can I ask – are attempts still being made to find a “super” TKI to combat Tarceva resistance, or have researchers turned their attention to drugs in combination, MET inhibitors, immunotherapies etc? In other words, has the afatinib experience inhibited enthusiasm for further research into TKIs, or is it just that it was the not-quite-right drug in an evolving category of drugs?


49-year-old non-smoker, dx stage IV NSCLC May 2010 (squamous tumour of the left lung with multiple brain metastases). Radiotherapy to chest and brain; progressed through two cycles carbo/gemcitabine. Repeated lung collapses; pneumonia in collapsed lung, Nov 2010; bronchial stent placed, Dec 2010. Declined second-line Taxotere. Mutation testing Feb 2011, surprise EGFR exon deletion 19. Started Tarceva (150mg), Feb 2011. Progression in liver and elsewhere, May 2013.

January 22, 2013 at 4:15 pm  #1252901    
Dr West
Dr West

I don’t think people have given up on either concept. They aren’t mutually exclusive concepts to test, so different trials will test later generation EGFR inhibitors, or “pan-HER inhibitors”, while others will look at combinations to inhibit several targets at once.

-Dr. West

January 22, 2013 at 5:04 pm  #1252905    

Yan

Certain Spring, it is really lucky that we got Afatinib as a compassionate drug. Our doctor initially didn’t want to apply for the drug, same argument saying it is no better than a placebo. But without applying for this drug, we have no candidate drug available in Canada unless to seek for clinical phase I trials. She was also very surprised to see the CT results showing significant shrinkage.

I don’t know whether she is now very optimistic or any other reason, that she hasn’t booked any CT scan for my husband since then ( which will be 4 months without CT scan). Now, she asks us to do X-ray every 2 months before the doctor appointment, which makes me feel a bit nervous.

April 15, 2013 at 12:39 am  #1255662    

sunflowerphil

I am Asian 71 yr old woman with EGFR exon 21 was on two cycle low dose cisplatin gemcitabine then switch to Tarceva 150 ml. For eight months. Had little progression my tumor grew from 1.7 cm to 2.4 cm and was very fatigued all the time. Stopped tarceva and got four cycle carbo, alimta and avastin then maintenance avastin and alimta only for another eight cycles. My tumor decreased to 1.7 cm again and progressed again to 2.4 cm so am now on Afatinib with Erbitux every other week. Now finished three months and my Sob increased not withstanding more side effects on skin, scAlp and nails. Can still tolerate but am afraid of my worsening SOB. What should be my next step? Before I was given Afatinib and Erbitux, my onc wanted me to go back to carbo alimta and avastin which I refused because of bad headache and fatigue.Do you have any suggestion DR. WEST? Please help me!

April 15, 2013 at 1:22 pm  #1255669    
catdander forum moderator
catdander forum moderator

Hello sunflowerphil, Welcome to Grace. We aren’t the type of place you want to need but we can provide good information that will help you make the best decisions for treatment.
I’m sorry but our faculty aren’t able to say what you should do, each person’s cancer is so individual those decisions need to be made by the doctors directly involve in your case.

This is a link that describes the best course of action for 2nd of later lines of treatment. At the end of the discussion is a list of links under, :for more information

http://cancergrace.org/lung/2010/10/04/lung-cancer-faq-2nd-line-nsclc-option/

Dr. West said this about using platinum after 4 or 6 cycles, “Yes. First, it is very customary to stop the platinum-based combination after 4-6 cycles, and there is no established benefit to continuing a two drug chemo combination beyond that point for advanced NSCLC. As the nurses said, such a reaction to carboplatin is common, particularly after more and more treatments, so continuing it beyond that point is problematic, and there are other treatment options to pursue.” from, http://cancergrace.org/lung/topic/carboplatin-hypersensitivity-reaction/

and our most recent addition to the library, Here’s the list of videos done at the International Association for the Study of Lung Cancer (IASLC) 13th Annual Targeted Therapies in Lung Cancer meeting. http://cancergrace.org/general/2013/02/20/iaslc-vids/

I hope this is helpful,
Janine

April 15, 2013 at 7:19 pm  #1255679    
Dr West
Dr West

I note that it seems you didn’t progress on either Alimta (pemetrexed) or Gemzar (gemcitabine), but rather discontinued them for other reasons, so I consider both of these options to still consider for the future. In addition, Taxotere (docetaxel) is an agent that has an established value in previously treated with advanced NSCLC. I would consider your headache to likely be caused by the Avastin (bevacizumab), the value of which is not clear at all, so perhaps returning to Alimta or gemcitabine, or else trying Taxotere for the first time, would be a strong consideration. And if there happens to be a trial of another option specifically for patients with an EGFR mutation and acquired resistance, that would certainly be attractive as well, though these trials aren’t readily available in most places.

Beyond that, it’s not appropriate for me to make an individual recommendation, so I think that it would be best to discuss these options with your oncologist.

Good luck.

-Dr. West

October 29, 2014 at 9:51 am  #1266783    

ashes123

Dr. West,
First thanks so much for helping others through the confusion of cancer/treatment. A question and comment. I thought afatanib results showed that if/when tarceva stopped working afatanib would work ? That is upside I see. Question. Asian wife, 50yo, non smoker, egfr positive with 790 and 858 mutations stage four, pleural effusion but no mets beyond single lung. diagnosed June2013. tried tarceva for 2 months no impact, carbo avastin alimta Oct to Feb 2014. Then avast/alimt maintenance. shrunk and stable CT today shows minor growth to three 4mm nodules (2mm to 5mm, 5mm to 11mm, etc.) but large tumors unchanged 3 X 4 cm. Love our oncologist but wondering. He suggests going to afatanib. I am wondering why not go to immunotherapy trial locally for Bristol Nivolumab because what I read …more you damage your immune system/health prior to immuntherpy then greater the chances immunotherapy may not work.

October 29, 2014 at 9:54 am  #1266784    

ashes123

I should add that I know with limited data it is hard for you to reply possible, but any thoughts would be appreciated. Also, CD 47 Stanford and OTS964 U of Chicago news…….hoping you saw these. I know you don’t know tonights lottery numbers but your guess as to when these get to phase II trials? Any hope for my wife. Should we limit sugar/carb intake and move to alkaline diet….or at this point your not convince it helps?

October 29, 2014 at 10:06 am  #1266785    
Dr West
Dr West

I don’t want to speculate about very early clinical trials — I put no faith in the hype from preclinical work; most of it translates to nothing, but it’s very easy to call everything a breakthrough because it works in preclinical studies.

As for afatinib, some people favor it, but I cannot understand why other than that it’exists. It is not because of any evidence. It is not an effective single agent therapy for patients with acquired resistance on erlotinib. The response rate is about 8%, which is about what you’d expect to see from just retreating with Tarceva after being off of it for a while. There is no evidence that as a single agent it is a meaningfully effective agent for acquired resistance.

-Dr. West

October 29, 2014 at 5:04 pm  #1266805    

ashes123

So may I ask what would be your suggested next option? If we have tried tarceva no luck, did six cycles of carbo alimta avastin which bought us a year……if your not strong on afatanib then what would be next best option? Thanks, and again I know you are answering with a lack of a lot of information but one more opinion is helpful.

October 29, 2014 at 5:56 pm  #1266806    
JimC Forum Moderator
JimC Forum Moderator

Hi,

There isn’t necessarily one best option. As far as traditional chemo, the three agents which are approved for second-line (and later) use are Alimta, Tarceva and Taxotere (docetaxel). Since you’ve used the first two, Taxotere would receive strong consideration as a next step. Other chemo drugs which are approved for first-line use and are often used in later lines include Taxol, Gemcitabene and Navelbine. Though the evidence is not as strong for their use after first-line, some patients do receive a benefit from them.

Aside from those choices, there are also clinical trials of novel agents, including immunotherapies. Since your wife did not respond well to Tarceva, there might not be much reason to try the acquired resistance trials, unless a specific resistant mutation is found in her cancer cells.

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

October 30, 2014 at 5:18 pm  #1266831    
Dr West
Dr West

We’re legally restricted from suggesting a treatment approach for someone who isn’t our patient. If you have a specific question about a treatment, we can address it as best we can, but we can’t answer open “what should I do?/What would you recommend?” questions, since that’s the specific province of your doctor +/- any second opinion consultations you might pursue.

Good luck.

-Dr. West

December 1, 2014 at 3:01 pm  #1267368    

ashes123

Dr.West,
As always…thank you so much for writing and replying. If I can ever do anything for you, please ask. Question. I was reading your NSCLC Mutation explanation thread. Excellent but left me confused in one area. My wife, stage iv nsclc, egfr positive. She is mutated in exon 20(790) and exon21(858). I understand 790 can result in resistance to TKI therapies. But does the 790 and 858 tend to be more or less responsive to TKI therapy? Again, I know 790 is a resistance to TKI therapy but not sure if your explanation of mutations is saying that if you have both 790 and 858 then you are better off, or worse off. Is this mutation combination better or worse then just having 790 alone or 858 alone.

Thank you.

December 1, 2014 at 3:45 pm  #1267369    
JimC Forum Moderator
JimC Forum Moderator

Dr. West discussed the situation of a patient having both an activating and resistant EGFR mutation here. He sums up the discussion by stating:

“Specifically, those who had an activating EGFR mutation and no resistance mutation had the longest progression-free survival (PFS), followed by those who had both an activating EGFR mutation but also a T790M resistance mutation, and then patients with no activating or resistance mutation having the least impressive PFS:”

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

December 1, 2014 at 7:21 pm  #1267372    
Dr West
Dr West

If the cancer has developed resistance to an EGFR inhibitor, having a T790M mutation is associated with slower progression in some studies compared with acquired resistance in someone who doesn’t have a T790M mutation (and therefore has a different mechanism for acquired resistance). It’s also clearly more beneficial to have a T790M mutation in the setting of acquired resistance now that we have agents like AZD9291 and rociletinib (CO-1686), in large clinical trials, at least, for patients with a T790M mutation, since they are associated with a high response rate of about 60%.

In patients who don’t yet have evidence of acquired resistance, it’s better to just have an activating EGFR mutation and no T790M mutation.

-Dr. West

Viewing 16 posts - 21 through 36 (of 36 total)

You must be logged in to reply to this topic.