Is the Subtype of Lung Cancer NSCLC important in establishing treatment options?

Mum has recently been diagnosed with lung cancer (NSCLC carcinoma). They have started her on chemo (Vinorelbine + Cisplatin). Handling it amazingly and will start her second cycle soon. Radiotherapy may also be added depending on PET scan results (should know this week).

We are concerned about whether the NSCLC carcinoma subtype (e.g. adenocarcinoma / squamous cell carcinoma) is important, as we were advised they didn't establish this from the biopsy results. From what I've read so far, it appears to be important to establish treatment options (e.g. chemo drugs / targeted therapy / immune therapy).

Can chemo drug choice / radiotherapy be dependent on subtype? Can option of targeted / immune therapy be dependent on subtype? Is it important to establish the subtype at this stage? Should we be asking to have this checked?

So much going through our minds at the moment.

Many thanks for any advise. I wish you all the best.

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  • Until recently there have been no therapeutic implications to further classification of NSCLC. However advances in molecular biology are improving the understanding of lung cancer and changing the approach to treatment.

    Now, more detailed testing can be done on your tumour if your doctor requests it. These tests are sometimes referred to as molecular testing, and may involve:

    •looking for changes (mutations) in the DNA make-up of the tumor

    •looking at levels of specific proteins present in the tumor

    Mutation analysis is becoming increasingly important with personalized therapy with treatment based on histologic subtypes (adenocarcinoma versus squamous) and the presence of molecular markers [epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK)].This information can affect the patient’s management, for example, choice of drugs.

    Some lung cancer treatments are called “targeted therapies” because they are designed to target specific tumour characteristics. It is important to know if you have a tumour with one of these characteristics so you and your doctor can make well-informed decisions about your treatment. Yes you should ask to have this checked. If the doctor is not requesting it he/she will give you an explanation as to why not.

    Some information which may be useful.

    golcmc.com/about-mutation-t...

    cancerresearchuk.org/about-...

    Kind regards,

    All at the Roy Castle Helpline

  • Thanks again for your response. Having done some further reading, there appears to be a trend between the choice of combination drug with a platinum based drug. From what I have seen, Pemetrexed appears to be recommended for non-Squamous and Gemcitabine for Squamous.

    I couldn't find anything related to Vinorelbine and a particular subtype. Is Vinorelbine generic for all NSCLC subtypes? I also couldn't find anything comparing Vinorelbine to the other possible combination drugs. If there is a relationship between combination drug and subtype, I feel concerned that there may be a more effective treatment available, but which one can't yet be established as the subtype is unknown.

    Could there be benefit in finding out the subtype, for treatment options now or in the future (inc. clinical trials)? If so, are there any recommended ways to do this (e.g. pathology second opinion of the biopsy sample)?

    I also read from NICE that Pemetrexed is only recommended for non-Squamous as a maintenance treatment if the previous combination drug was Gemcitabine, Paclitaxel or Docetaxel. Is it possible to have Pemetrexed after Vinorelbine?

    Keeping fingers crossed that the molecular analysis results open up the option of targeted therapy too. Hoping to keep options open.

  • Hi GH86 - so great to hear your Mum is handling it so well. My Dad was recently diagnosed with Stage IV NSCLC adenocarcinoma, which was a terrible shock. They analysed his cancer cells (from pleural effusion) and found that they have a specific mutation that can be attacked by specific medication - this is targeted therapy, which he is now on (Gefitinib).

    From what I have read and understand (not a doctor), targeted therapy has less side-effects than chemo, as it is more targeted to the cancer cells. Adenocarcinoma tends to affect never-smokers, while squamous cell tends to affect smokers. The cancer cell mutations also vary depending on the patient profile, and there is often a high chance there is no mutation at all (which means targeted therapy would not be an option).

    It may be worth talking to your oncologist about molecular analysis of the cancer cells, and understanding the probability of having a mutation, and the different outcomes expected from the treatment options available.

    ps: I researched immunotherapy as well, and was told by the oncologists that this would be more suited to second-line treatment or third-line later, when the targeted therapy stopped working, so they were reluctant to talk more about it at that stage.

    ps: Macmillan/Roy Castle have fantastic resources to understanding lung cancer which I devoured and much more publications.macmillan.org.uk/

  • Many thanks for your responses. Lostsheepie - Happy to hear your Dad had a match for a targeted therapy. I hope it's working out well.

    We had an appointment with the Dr this week and brought up the subject of targeted therapies. They advised that the original sample has been sent for molecular analysis, so they started looking at this straight away. However the results have not yet arrived. How long should it take to get these results?

    Mum is a non-smoker, so believe adenocarcinoma is more likely, but the pathology report didn't confirm the cell subtype. Might this come from the molecular analysis, as well as mutation and protein levels?

    Dr advised that radiotherapy should be added to our treatment plan and targeted therapies may be an option afterwards. Keen to ensure all relevant information is available to avoid any delays

  • Hi GH86 , in my Dad's case it took 1 week to confirm the pleural effusion sample was malignant, and then another 2 weeks for the results of the molecular analysis, so 3 weeks total. Our oncologist who saw us after the first week was very helpful and they told us they followed up with the lab two times to try to get the results back in a timelier manner (which took 3 weeks total). The lab did test for around 20 genes, which is why it possibly took so long.

    They already knew it was NSCLC adenocarcinoma after the 1st week, and the full results after 3 weeks gave us the specific mutation.

    Hope this helps! Be positive and strong for your Mum!

  • Great to hear your results came pretty quick. It must be reassuring to know when further options open up. I read that Gefitinib is for EGFR positive results, for which there are a few treatments available. I hope the treatment is going well with no side effects.

    It's been a fair bit longer for us since the biopsy, so I am on the phone this week to chase it up.

    Thanks for your kind words. Keep up the positive momentum, for both your Dad and yourself!

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