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?

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.

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

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.

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

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

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.

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