bone650
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I have had surgical resection and have just completed chemotherapy. I have EGFR 858 mutation I was planning on getting into a trial for Osimertinib but was told I don't qualify because because my creatinine runs 1.8-1.9. This turns out to be true for the Alchemist study also where I might received Erlotinib. Neither drug is metabolized in the kidney or would require adjusted dosing. The inclusion of this requirement seems quite arbitrary and I don't know how to proceed. Do I just wait and see if I am in the 50% who survive or the recurrence group?
I would also like to know your feelings about being followed with serial assays for tumor DNA.
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Reply # - July 30, 2018, 08:11 AM
Hi bone650,
Hi bone650,
Welcome to GRACE. I was in a somewhat similar position when I finished adjuvant chemo following surgery.
I went into a clinical trial of additional adjuvant immunotherapy (durvalumab). Unfortunately the first dose knocked out my thyroid and I declined to participate further in the trial, fearing further side effects with no clear benefit.
This is the main reason clinical trial criteria especially in the adjuvant setting are so strict... the possibility of adverse side effects without a clear benefit. After all if the benefit were clear, there would be no reason to do the trial.
Since then it has been surveillance with ct scans. Blood biopsies for detecting early stage lung cancer are an area of active research but nothing has been approved by the FDA for this purpose yet. The efficacy of course will depend on what signatures are examined in the test. For a discussion of investigational trials see:
Blood test shows potential for early detection of lung cancer
June 3, 2018, Dana-Farber Cancer Institute
https://medicalxpress.com/news/2018-06-blood-potential-early-lung-cance…
It's a bit unclear how effective different immunotherapies are for people with specific EGFR mutations, but that is the only other option for a clinical trial I am aware of besides ALCHEMIST as adjuvant treatment for early stage lung cancer.
How often are you being followed with ct scans?
Reply # - July 30, 2018, 08:20 AM
HI bone650,
HI bone650,
Welcome to GRACE. It's good to hear that your cancer was discovered at a relatively early stage and that it has been successfully resected. After surgery and adjuvant chemotherapy, the role of immediate subsequent targeted therapy is unclear. As Dr. Heather Wakelee states in this post, trial evidence tends to show that while immediate use of targeted therapy may extend the time to progression, overall suvival is not improved.
As far as the kidney issue, the prescribing information for erlotinib does discuss problems with renal impairment (section 5.2), while the prescribing information for osimertinib states that
"No dedicated clinical studies have been conducted to evaluate the effect of renal impairment on the
pharmacokinetics of osimertinib. Based on population pharmacokinetic analysis, no dose adjustment is
recommended in patients with mild [creatinine clearance (CLcr) 60-89 mL/min] or moderate (CLcr 30-59
mL/min) renal impairment. There is no recommended dose of TAGRISSO for patients with severe renal
impairment (CLcr <30 mL/min) or end-stage-renal disease." (Section 8.6)
I'm not certain I understand the context of your serial assay question. In terms of checking for progression, follow-up CTs are the norm, and if progression is detected, then a liquid biopsy may be performed and tested for mutation changes, although a tissue biopsy is still preferred if fesible. Liquid biopsies are becoming more popular to track subsequent changes in mutational status.
JimC
Forum moderator
Reply # - July 30, 2018, 08:53 AM
That is very well put, as
That is very well put, as usual, Jim. Thank your for your clear explanations.
Reply # - July 31, 2018, 12:08 PM
Thanks for your replies Jim
Thanks for your replies Jim and Mark. Sorry to hear about your wife Jim. I also was not a smoker. Until I was diagnosed I never realized how prevalent this disease is. I was greeted by physicians who told me that so much is happening that's exciting as far as treatment of this disease. As I get on and my treatment and research I see that there is much that's promising but not a lot that's changed yet. When you know that there is approximately a 50% recurrence and progression rate after the initial surgery and chemotherapy it's not easy to be passive about trying other possible remedies. I am still going to pursue getting into the Tagresso study as from what I'm hearing this drug does seem to have a significant effect. I am not a candidate for immunotherapy as I had Wegener's granulomatosis six years ago successfully treated with Rituximab. Having any autoimmune condition would exclude me from the immunotherapy studies. I have also heard of cases such as yours Mark with thyroid injury or pancreatic failure.
My oncologist follows his patients with six-month interval CT scans. I am scheduled for September. I learned about and became interested in the serum assay for tumor DNA after meeting a biologist at a cocktail party who is involved in a research lab at Massachusetts General Hospital and has worked on this type of testing. He is a strong proponent of this as a screening test as he felt that the sensitivity of these studies has improved significantly. He did say that no insurance company was yet willing to pay for it unless recurrence was already diagnosed and standard biopsy was not appropriate.
I am meeting with my oncologist again next week. Our first post chemotherapy session. He is smart and caring and said he would contact study directors and see what could be done. I appreciate your responses. It's good to hear other's experiences and thoughts.
Michael
Reply # - August 1, 2018, 10:34 AM
Unfortunately, the statistics
Unfortunately, the statistics on recurrence after resection with or without adjuvant chemotherapy are what they are and this is also what prompted me to get into a clinical trial of adjuvant therapy.
Why were you staged 2B? I was initially staged that way until new guidelines came out for multifocal lepidic type lung cancer and was restaged to 1B... Did you have lymph node invasion?
I'm glad you were able to successfully treat your Wegener’s granulomatosis. Given you are EGFR+, having an auto-immune disease like that is an additional reason to put immunotherapy onto the back burner.
I live in Canada where the options for testing are still limited. If I got a recurrence I would send it to Foundation One to get a more complete description of the tumour and then try to petition my insurance company to pay for part of it. Non-invasive tests for screening of lung cancer are also being developed. I think the tools for observing 'high risk' patients who are currently being monitored with regular ct scans is going to change in 5 years.
I found a 2018 peer reviewed short paper you might be interested in if you haven't already seen it:
"Adjuvant epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) for non-small cell lung cancer (NSCLC): A systematic review and meta-analysis"
The conclusions are:
" Adjuvant TKIs significantly decrease the risk of recurrence in EGFR-mutant NSCLC patients but do not improve OS. Yet, OS data are still immature and longer follow up is needed for a definitive assessment of this outcome measure. Further results from ongoing well-designed trials will define the role of adjuvant TKI in NSCLC and provide stronger conclusions."
I hope your oncologist can find a way to get you onto an adjuvant TKI and that you tolerate the medication without too many side effects.
OTM
Reply # - August 4, 2018, 09:43 AM
Hi Michael,
Hi Michael,
Apart from the unresolved question of whether adjuvant TKI therapy will improve overall survival as well as time to progression, there is another factor that may be considered when deciding whether to move forward with such therapy...quality of life. Although the majority of patients quite understandably want every bit of cancer out of their bodies as soon as possible and be cured, the data does not yet show that adjuvant TKI therapy increases the chance of accomplishing that goal. With that in mind, the value of a treatment break cannot be ignored. If adjuvant TKI therapy only delays progression, then at some point further treatment will be needed, leading to an uninterrupted course of anti-cancer treatment, from surgery to chemotherapy to TKI to whatever therapy follows.
Treatment breaks can allow the body time to recover from the side effects of prior therapy, and many patients enjoy their time off treatment. The decision is one of personal preference, and there is no right or wrong course of action. From personal experience with my wife's lung cancer (which was in the very early days of EGFR TKI therapy), after first-line chemotherapy we elected to switch immediately to Tarceva, and she was never off-treatment for the remainder of her cancer fight. Although there are times when I wish that she could have enjoyed that break, I know how we felt at the time, and neither of us had any doubt that we wanted to keep treating and start Tarceva.
I simply put this issue out there for anyone who is facing a similar decision.
JimC
Forum moderator