Raz and participants discuss when and how to use osimertinib based on available evidence
During a targeted oncology case-based panel discussion, Dan J. Raz, MD, MAS, and his peers discussed the challenges of lung cancer screening and treatment.
Reset: Do any of you encounter any barriers to treatment, such as a lack of tissue or tests that take a long time? Do you have an in-house test, and where do you send it?
MARLA: We have no particular difficulties when we send them for testing. In my case, I can say that there are no specific challenges, but generally our oncologists order the tests because the patients all have an established oncologist that I would let the tests order.
PAUL: We generally have an automatic system. Anyone who gets resected and has adenocarcinoma automatically gets EGFR, ROS1, and PD-L1 test. Until recently this was pointless as there was no actionable data to use it on, but recently things have changed. But we never had a backlash. I think the biggest challenge is that we send each of these tests to 3 different labs to get a response for our samples, and it’s not very efficient, it takes longer, and it’s probably best to do it. send to FoundationOne or another large lab or, if you are in a university center, do it yourself. I think the next real challenge is to make sure one of these specimens is sent and made together.
Reset: You are doing a more limited panel. If these tests are negative, do they send the sample for NGS [next-generation sequencing], or is it just in the metastatic setting?
PAUL: They haven’t really done it for early-stage lung cancer screening – sending NGS – but there are other indications you could potentially act on. They do this at stage IV or advanced stage. My guess is that if you’re going to do that, you might as well do NGS for the whole specimen and then you’re done. One of the obstacles is that sometimes insurance companies don’t want to pay without any indication.
Reset: In my hospital, we have an internal test, and these have a second internal test, but it’s complicated, and it takes a long time to get results. However, I have noticed less of an insurance problem just recently over the past year or so. I don’t know if other people have been through this, but it seems a lot of insurance companies are covering everything now. Is it pretty much just the oncologists ordering the test, or does someone here order the test when the pathology returns?
MARLA: For us, it’s automatic, so it’s initiated by our group to do that and it’s done automatically.
PILUIKO: Same thing for us. It’s an automatic test, but usually the oncologist takes care of everything, so we don’t have a lot of problems doing the test.
Reset: For patients like this with large tumors, are any of you doing neoadjuvant therapy here? In my facilities we have several neoadjuvant trials, but do any of you administer to patients with clinically N0 tumor that is largely neoadjuvant therapy?
PAUL: We do in some cases. If someone has a large tumor, is young enough, and is performing well, then we will consider doing it.
MARLA: In our establishment, most of the time not, especially with the N0.
Reset: Do most of your patients see an oncologist before seeing you, or how does it work? Or do you send patients to an oncologist before if they’ve never seen one?
MARLA: Usually they always see an oncologist, even if it’s a simple diagnosis of stage I cancer. Sometimes, if they can’t fit in and are ready to go, we let’s go directly to the operation and then they will see [the oncologist]. Usually, we try to get them to establish their stage first with an oncologist.
PILUIKO: I would say that at least 70% of my patients already have an oncologist on board, and if they haven’t seen him before seeing me, they will see him before the operation.
ONUGHA: Yes. Most of the time, our patients see the oncologist before surgery, unless they have advanced disease. Most of the time they are referred to us and then we see them and we usually schedule surgery. Once we get the results of the pathology, we send them to the oncologist.
PILUIKO: Very impressive data – I have a question, however. How do you explain that there is such a dramatic difference between disease free survival and overall survival [OS] is so poor?
Reset: I think part of the problem is if you look at the number of patients at risk, as you get to 3 years old, there is a very small number of patients because we don’t have any. This study was also stopped prematurely because there was such an impressive change in disease-free survival, and that was the main result.
They started with 233 and 237 patients in [the osimertinib and placebo] arms, respectively, and at 3 years, we came down to 39 and 33 patients; at 4 years, 1 patient remains. So I don’t think it’s necessarily deaths, but there haven’t been a lot of patients who have been in this study for over 3 years. I think there is a big question mark in the long run, what these curves will look like.
PAUL: I think it’s a statistical thing. You don’t have enough events to differentiate.
Reset: I agree with you. On top of that, survival is really good in both groups.
PAUL: I think one of my issues with this non-bone study is that it’s only in patients who have had one or more lobectomies. There are therefore no patients who have undergone sublobar, wedge or segmentectomy resections. I don’t think they, at least in the journal, have anything about the quality of the surgeries – how many lymph nodes were taken, how many stations were biopsied. I think there is some of that data, but not all of it.
Reset: [Lobectomy or greater] makes sense because these are patients with IB and higher disease. So probably not the type of patient you would generally do sublobar resections for. But I think it’s an interesting question: How does this therapy make a difference in patients who don’t have the best lung function? Can you [do] not anymore now that we have this drug?
Do you have other concerns about the OS? [Will you wait to use this, or will you give osimertinib to all eligible patients?]
SCHWARTZ: I think it will depend on the oncologist where I work. We are going to consult them and think about it, but we will not be pulling the trigger to give them this drug.
MARLA: Much depends on where you work, depending on your oncologist. But in my house, I think they are definitely considering using it in all eligible patients. At least most oncologists who see patients with lung cancer [would].
Reset: Generally speaking, if you follow the book for stage II and IIIA patients, they should receive cytotoxic chemotherapy and then adjuvant osimertinib for 3 years after that. Have any of you had the experience of treating patients like this where the oncologist may have skipped chemotherapy and gone straight to osimertinib? Or have any of you seen, for those of you who have had patients who have received adjuvant osimertinib, patients who have received chemotherapy? [first]?
ABRAHAM: Most of our oncologists are fairly conservative… so they give them standard cytotoxic chemotherapy and then try to give it under other circumstances. I think a lot of them look for OS data before doing anything, and I think the last thing is it depends on where you’re going. You go to places where they don’t quite follow the National Comprehensive Cancer Network guidelines: “This product is less cytotoxic, so I’m going to give it to all of my patients. Why not?”
PILUIKO: I think our oncologists are very aggressive with this, so I think everyone who qualifies should probably get it.
Reset: We first ask this question about chemotherapy. I spoke to one of the oncologists who is sitting with me in the clinic and I asked her about it and she said, “No, we have to follow the book” and then I referred a patient to her. who turned out to have EGFR-mutated disease that had stage II lung cancer, and I saw the patient a few months later, and she received osimertinib without chemotherapy. I asked the oncologist and said, “I thought you were going to give chemotherapy first,” and she said she was a healthy woman and she really didn’t want to. chemotherapy. It will therefore be interesting to see in practice how this is achieved.
What about — I know again it’s the oncologist’s prescription — but have you heard of insurance issues, for example? It is a very expensive drug; often these drugs have high co-payments. Have any of you heard any complaints from patients about the cost?
ABRAHAM: Yes. We have certainly encountered this as stated in our tumor committee regarding the cost and the prohibition for patients to access it.
MARLA: I hear that from time to time. Most of the time, they don’t mention the costs on the tumor panels.
PAUL: I think it’s pretty new to use in this setting too, so I don’t think people have a lot of experience.
Reset: Does anyone work in underserved communities where insurance plans are perhaps much more restrictive?
PAUL: Our healthcare system covers an intercity hospital in Newark, New Jersey, where many people either have some form of Medicaid or no insurance, and oncologists are trying to charge drug companies or their state for it. cover, but often this is limited. You don’t get the state of the art, unfortunately.
Reset: What about stage IB patients, given the lack of data on OS? Many of you have commented on the oncologists who made the decision, but what’s your opinion? How excited are you or your oncologist to use [osimertinib] in IB disease?
PAUL: I think it depends on the wait for the operating system data. I think in some cases they will have it. The oncology group I work for said they would give it to patients if they have a high risk of recurrence, like the size of the tumor or certain characteristics of the tumor. They will administer cytotoxic chemotherapy followed by it if necessary.
Reset: Do you present all your patients to the tumor board or do you selectively present patients to the tumor board? I know it is different in each establishment.
ONUGHA: Yes. We selectively present patients to the tumor board.
MARLA: We present all cases, even if it is just step I.
1. Wu YL, Tsuboi M, He J, et al; ADAURA investigators. Osimertinib in EGFR resected non-small cell lung cancer. N English J Med. 2020; 383 (18): 1711-1723. doi: 10.1056 / NEJMoa2027071