Nivolumab for EFGR t790m+ possible? - 1287985

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coco1
Nivolumab for EFGR t790m+ possible? - 1287985

I have a few questions I would appreciate to be answered pls before I see if I go back to my Mother's oncologist as I feel not enough was done. NSCLC EGFR+ t790m+ never smoker on tarceva 2 years, rib biopsy and pleural tap for AZD9291, pleural drain in hospital, catheter installed, caught infection (from initial procedure or hospital!?) trial closed, 3 rounds of alimta/carboplatin eventually got AZD in late jan this year, passed away a month later.
Frustratingly enough, there was an article in the local newspaper the other week with her oncologist saying that Nivolumab (Opdivo) would now be rolled out in our area in Scotland and how it can double survival rates of lung cancer. Is this true for NSCLC adenocarcinoma, Egfr + never smoker? I have read mixed messages concerning it for these types of patients. Her oncologist told us after she had passed that this would have been her next treatment, I don’t know if it is at clinical trial stage in the rest of the world or available?
As much as we appreciate the NHS, I feel in the States there are more options, ironically 13 years ago we were living in Houston. I notice Afatinib and Iressa (Gefitnib) are not licenced on the NHS in Scotland but I assume they work in a similar same way to Erlotinib and wouldn’t have been an option? We would have happily paid for treatment, if I knew it would have kept Mum alive, or going privately even if drugs had cost £20k or £200k. Mum really trusted her oncologist although I know once her oncologist said to her she wondered if she made the right decision. She left her last March although Mum was getting more and more breathless and we knew the Tarceva was not working. Going to the States perhaps would not have been feasible but going to Europe to get the drug or other trials in the UK or Europe to get a second opinion?
I know everyone is unique but I would appreciate feedback please so that I can close the chapter on this. Thanks

coco1
March 2013: Right upper lobe

March 2013: Right upper lobe 3.0cm x 2.4cm reduced to to 2.4cm x 1.7cm, 6mm nodule reduced to 4 mm
6mm nodule in left lower lobe also 6mm but semi-solid
Mediastinal and hilar lymphadenopathy has resolved and nodes now measure within normal size limits
Right paratrcheal nodes previously 19mm short axis now 8mm.
March 2014 (ref to previous scan in 2013 I do not have)
Right upper lobe mass not changed significantly, 2.2 x 1.1cm -> 2.1 x 1.1cm
Right lower lobe 0.4cm (unchanged)
Left lower lobe reduced (0.8cm -> 04.cm)
No significant improvement (her oncologist wrote – no deterioration either!)
July 2014:
Right upper lobe 2.8cm
Smaller nodular density in right major fissure unchanged 4mm

Previous nodule in left lower lobe reducing in size
Right upper lobe measuring 6mm
The primary lesion in right upper lobe and subcentimtre right hilar and mediastinal lymph nodes are unchanged, progression of at least 3 small nodules in lung parenchyma.
June 2015:
Comparison to march 2015.

The primary tumour anteriorly at the right lung apex now measures 3.4 x 2.2cm. previous 2.7 x 2.5 cm. Right pleural effusion increased in size. There are multiple pulmonary opacities in the left lung which have increased in size and number from the previous examination in keeping with pulmonary metastatic disease. Similarily futher pulmonary nodules are now noted within the right lung together with some fissural nodularity. The largest pulmonary nodule in the right upper lobe previously measuring 10mm now measures 12mm.
The enlarged right hilar, subcarinal and contralateral mediastinal nodes measure at the upper limit of normal at 10mm short axis.
There are some new low attenuation lesions within the liver which measure up to 12mm in size keeping up with liver metases. Normal appearance of the adrenals, kidneys and pancreas.
No bony findings of note. The primary tumour at right lung apex has further increased in size, as have the bilateral pulmonary metastastes

coco1
and the right pleural

and the right pleural effusion with pleural thickening and fissural nodularity. New liver metastates identified. Progressive disease.

I've added some notes in above, By June Mum did wonder if her oncologist had left her too late. We knew Tarceva wasn’t working and she was becoming more breathless. This is when she had the 1.5l of fluid drained by thoracentesis and biopsy from rib to see if she had the mutation. Sent home in pain. In hospital twice to get fluid drained again, eventually catheter installed. Didn’t get the results of CT Scans from here on, we were told it had spread to bones when she was in hospital for about 4 weeks in the summer with serious infection which I don’t know if was caused by the thoracentesis and biopsy or from when she was in hospital to have the fluid drained (twice)?? 3 rounds of chemo ( alimta carboplatin), scan, was told it had worked but she didn’t get any more. Just on Tarceva. I don't know whether from the above it can be seen that the cancer was aggressive?

I just fear the time she waited for the drug let it go out of control and AZD didn't work. We never got the CT scan results from October, we were told that chemo had worked but she didn't want to put Mum through any more. I just wonder though if her tiredness, etc was due to the cancer rather than the chemotherapy? I remember coming home once to find her in tears as the district nurse was telling her her symptoms might have been due to the cancer progressing rather than chemotherapy. I told her not to listen, that her cancer was different and when she got AZD9291 she would get better, then there would be another targeted therapy, then another one…

Thank you for reading

JimC
coco1,

coco1,

Despite the detailed information you have provided, no one can say whether better treatment choices could have been made. Your mother's medical team were in possession of all of her medical records, including lab results and scan images and reports, as well as an opportunity to assess your mother's condition in physical examinations. In most cases when lung cancer is largely under control, a delay of a month or two in changing treatment in response to evidence of new progression does not have a significant impact on survival, but in those cases in which the cancer begins to progress rapidly in several locations, there isn't a treatment which can halt that aggressive growth and spread.

You are correct that neither afatinib nor gefitinib tend to be effective when EGFR+ lung cancer becomes resistant to Tarceva. As we have discussed in one of your previous threads, some patients simply do not respond to AZD9291 despite a confirmed T790M mutation. Responses tend to appear fairly quickly, but it's impossible to say whether starting it earlier would have made a difference.

Immunotherapies such as nivolumab work very well for certain patients, at a rate of perhaps 20-30%, but response rates for EGFR+ patients tend to be much lower.

Often there is no single course of treatment which is obviously correct in a given situation, and at times despite our best efforts it's not possible to stop an aggressive cancer. I experienced that with my late wife's lung cancer, which remained relatively under control for the better part of 3 years, only to suddenly appear throughout her body, including brain, liver and bones. Despite having an excellent oncologist and medical team and my being a well-informed advocate for her, no treatment was successful in slowing the rapid growth of her cancer.

Many of us who have lost a loved one to cancer have had similar doubts about treatment choices. I hope that you can find some peace of mind in the coming days.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

coco1
Thanks Jim for your reply,

Thanks Jim for your reply, one last question: I've heard of EXON 20,21, insertion/deletion genes, are these tested through biopsy or if you have EGFR+ t790m+ is it not possible to have these?

I guess we won't know where she got the infection from, the hospital will just say that that is a risk of being in hospital and it wasn't until later we realised how serious it was. As you say we will never know if the pleural tap had been done differently and the catheter or the drain installed straight away would she not have caught the infection and able to get AZD quicker and further treatment. It was 8 months of waiting until she got AZD9291,I don't know whether the t790m+ mutation changes if left with no treatment or if she already had an additional mutation such as C797S which affected it? She was in hospital a few times with pulmonary embolisms and infections (I worry sometimes it was due to me not being fastidious enough preparing meals, cleaning, etc or the fact I went back to work after the Christmas vacation surrounded by people with colds and coughs) although she bounced back I feel these may have weakened her further making treatment less effective. My friend who is a doctor (although my age and not specialised in oncology at all) told me once a cancer spreads there's little you can do which I told her is false as if you have the mutations you can control things for a while. However, perhaps it was just aggressive and the cancer would have responded to chemo better had it been controllable and AZD would have worked despite having it at a late stage and after waiting approx. 3 months with no treatment minus tarceva.

And of course, it's wondering what triggered the gene to express itself in the first place - diesel pollution, etc? and the fact by the time she was diagnosed it was stage IV and had gone into her lymph nodes. She did have the cough for a while and I just wonder if it had been caught earlier.

coco1
It's an awful disease to get

It's an awful disease to get and here at least there is a lot less funding into it as opposed to breast cancer, etc due to stigma originally attached that only smokers get it. I guess even by the time you present symptoms the cancer has perhaps already progressed further than you would like.

I guess I feel let down by her oncologist slightly, she always named my Mum as one of her 'special' patients due to the fact she was fit and healthy (until last summer!) and had the right gene mutations, perhaps we put her on too much of a pedestal but the other patients on AZD9291/Tagrisso are doing fine. She did say to her once she wondered if she had made the right decision but you put your faith in doctors and the medical staff.

I expected to get a letter from her oncologist but there is still nothing. I was so sure Tagrisso would work, even though she had been struggling to get up out of her bed and seat, that we left her in hospital that evening, not realising that she would be gone less than two hours later. I feel like I let her down, she asked my Dad if she was dying and he said no, the doctors weren’t overly clear, looking back now I think the nurses were trying to tell us but I always thought she would be ok even though we knew when she was diagnosed that it was terminal.

Take care, Jim

JimC
Hi coco,

Hi coco,

In answer to the question at the beginning of your posts, when EGFR gene testing is performed any EGFR mutations will be noted, including exon 20 and 21, and some patients do have more than one mutation present.

You've expressed many of the same doubts I felt during my wife's battle with cancer and after her passing. The whole process is just a very difficult thing to wrap your mind around, and there are elements of anger and guilt along with the sadness. But although our medical knowledge and treatments have improved, we wage an unfair battle with cancer and often, despite the best efforts of medical staff and caregivers, cancer is just too tough an opponent. I also wanted to know what caused her, a never-smoker, to get lung cancer. Though I have a number of suspicions, I will never know for certain, and that in itself causes pain and makes it difficult to accept.

I will also say that my wife's passing (and that of other lung cancer victims known to me) was similar in that when the next shift of her palliative care team came to the unit that day, they were shocked to learn that she had passed. No matter how prepared you think you are, you're really not.

All I can do for you on this forum is share my own experiences and thoughts, but you don't really think you're way through this. It's your heart that's broken, and though your mind tries to find a solution, it can't find one. Your heart just needs to heal, and that takes time.

My hope for you is for peace and comfort and healing.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

coco1
Thanks Jim for a

Thanks Jim for a comprehensive and compassionate reply. I went to see my GP (family doctor) on Friday to see if there was a letter from her oncologist. There wasn’t exactly but there was one from her dated 1st April, just after my Dad and I had been to see her oncologist at the hospital basically saying she was distressed at how I was and thought I might need some professional help. The doctor did not show me the letter before, despite me being there in April, counselling here usually doesn’t kick in till 6 months post bereavement. She ended it by saying she was sorry she could not have done more.

My GP had access to my Mum’s medical records and had a look at her scans post chemo and in January and told me that the cancer had been progressing in the bones and liver, although she admitted she wasn’t an expert at reading scans; her oncologist told my Mum that chemotherapy had worked but she did not want to put her through anymore. Mum did wonder why she did not have a copy of the scans, but hoped chemotherapy had zapped the cancer in the bones. I remember once Mum saying her oncologist had medical students in and Mum had vomited previously that day, and she asked them what they thought was wrong, one of them suggested the liver but her doctor said, No her liver is fine. I guess it’s just this conflicting information, I’d like to know the full story? I also assume that it was not BAC form of adeno as when she was first diagnosed it had spread to lymph nodes? I just think they left the cancer to spread but I suppose if chemotherapy was doing more harm than good and the drug wasn’t available, there was nothing else they could do. I guess I could have been more prepared but we had such hope in AZD9291, as had her oncologist, unlike the rest of the medical team. These are the types of questions I have for her oncologist, although the GP doesn’t think meeting her again will help. I also suppose getting infections, pulmonary embolisms, etc can happen when the cancer

coco1
weakens the body although I

weakens the body although I feel the pleural tap could have been done differently in the first place meaning she might have not got the infection and got the drug earlier but the outcome may have still been the same. I believe her biopsy was sent to Astra Zeneca for testing for t790m+ so I assume they would have communicated to her medical team if there had been any other mutations? And her oncologist would have let us know if there were other options of getting the drug quicker/different trials. I suppose I feel bad, thinking now of how extensive her cancer was, and how I was not always understanding, as I truly believed that she would get better.

catdander
HI coco 1

HI coco 1

The unfortunate irony of hospital is that while they allow medical teams to heal people they are also perfect breeding grounds for infections. Every invasive procedure done carries a possibility of contracting an infection. In fact the hospital is an excellent place for infections to acquire resistance to antibiotics that allow them to become stronger. As you alluded to a person's weak condition makes the body less able to fight infection.

It's very common not to be able to tell why a person is declining, whether it's due to cancer progression or debility due to treatment or another co-morbidity such a infection. The important issue is to know when the scales have tipped in favor of not treating. It sounds like your mum's oncologist was an advocate for her continued health for as long as she could. The balancing act to know when to stop treatment is one with which I've struggled as a daughter and I marvel every time I think about our oncologists who do this everyday. I hope you are able to give your mum's oncologist the benefit of a doubt, that she made wise decisions when treating mum even when not treating was the best treatment.

When people have PE it's common to drain them one or 3 times in hopes of it becoming stable before making the decision to put in a catheter.

I'm sure one can go on for ever questioning all the steps taken in treatment. It's sounds as if you have the intellectual understanding that your mum was treated as well as possible but still you look for answers that can sooth the grief. As I think Jim said there are no answers that will help. Perhaps your mum's oncologist's suggestion that you seek therapy is one in which you can use to access bereavement counseling through NHS instead of waiting longer. She's seen people in your shoes far too often but it does give her a sense of how you're doing compared to others.

I wish we could be of more help.

All best,
Janine

coco1
Hi Janine,

Hi Janine,

The PEs Mum got was much later on in her treatment, the draining of fluid was done last June/July/August time 2015, the PEs were more November/January time when she already had the catheter installed. She was often admitted to hospital a lot later than she should have been. I didn't realise there was a disadvantage of putting in the catheter straight away.

It is good her oncologist was in favour of giving her AZD9291,the whole problem was the waiting for the drug for ca. 8 months, knowing there was something out there. I guess she weighed up the options of chemotherapy doing more harm than good, even though the alternative was no treatment whatsoever (minus Tarceva which hadn't been working for over half a year).

I guess I have to think her oncologist did what was best although she didn't see her often and that the cancer would get her in the end, just a couple of years earlier than I expected.

catdander
The reason many oncologists

The reason many oncologists don't want to install a permanent cathater is it leaves a permanent opening into the lung into which infection can enter. It's hoped that the PE won't return however if it does a catheter can be the best choice.

I'm so sorry we're not able to help determine if your mom's oncologist treated her to the best extent possible. But I do hope you find peace in the coming months.

Janine

coco1
Thanks Janine, I thought the

Thanks Janine, I thought the PE was just a symptom of the cancer and due to lack of mobility, etc. As far as I recall, Mum's catheter worked by a pump in that it was closed off meaning that the nurse had to come in each time and open it up when fluid needed to be removed? I remember once asking about infection but was assured that no infection was possible as the system was normally closed off or something to that extent.

JimC
Hi coco,

Hi coco,

The presence of the PE is an indication that cancer cells have spread to the pleural fluid, through the bloodstream. Those cells cause irritation to the lining of the pleura, which results in fluid buildup. Although the pleural tap is closed off except when draining is being performed, the catheter itself remains in place in the incision made when it was initially inserted. So although it is unlikely that infection could occur through the catheter, the presence of an incision, which can't completely close up due to the presence of the catheter, can allow the possibility of an infection to enter.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

coco1
Sorry Jim, crossed wires here

Sorry Jim, crossed wires here when I was referring to PE I was refering to pulmonary embolism that Mum also had a couple of times in hospital later on which I did not necessarily realise the severity of that. She got over them though and came home fine and had daily injections of daltaparin.

Re. the pleural effusion I did not realise that it was result of cancer cells spreading through the blood stream I assumed it was the tumour irritating the lining of the pleura. Does recurrent build up therefore mean a more agressive cancer? I'm sure I read somewhere that is not necessarily the case. Spreading to the pleural fluid doesn't mean the cancer is in the blood though I assume.

JimC
Coco,

Coco,

A recurring pleural effusion can be the result of an aggressive cancer, but not necessarily, so an increase in the size of an effusion, by itself, is not usually considered clear evidence of cancer progression. There can be enough residual scarring in the pleural lining to continue to cause fluid buildup.

The presence of cancer cells in the pleural fluid does indicate that cancer cells are in the bloodstream, which is why such cancers are categorized as stage IV.

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>