Lung Cancer Update, Issue 3, 2016 (Video Program) - Video 23Case discussion: A 68-year-old man and former smoker with Stage IIIA pan-wild-type NSCLC
7:23 minutes.
TRANSCRIPTION:
DR MOK: This is a 68-year-old man, ex-smoker. Now, the CT scan showed a left upper lobe mass, and that would confirm there was chest mediastinal lymph node involvement. So they’re Stage IIIA. Biopsy EGFR-negative and ALK-negative. So, naturally, the patient would not be eligible for any of the TKIs. So the only so-called treatment available for this gentleman would be the concurrent chemo/RT. But the question is, should you give neoadjuvant treatment first, or should you just go right into concurrent chemo/RT? DR LOVE: Actually, before you get into that, you mentioned that he didn’t have any targetable mutations. If he did, would you do anything? I mean, there are trials looking at up-front targeted therapy before chemoradiation. Would you do that outside a study? DR MOK: Yes. Let me explain. Okay? So it’s very tempting. I mean, come on! You’ve got a drug that can reduce the tumor size by a 70% chance, and the toxicity is low. I mean, with chemotherapy you can reduce it by about 30% to 40%, but then there are toxicities. So although there’s no trial — one of the reasons why there’s no trial is because the number of patients who are Stage III mutation-positive is very small. So, actually, in my practice — not in this case, but in other cases — it’s not uncommon I do give them a neoadjuvant TKI, and then I consider operation, because some of the responses are so dramatic. And so basically a lot of these patients with TKI-positive, then — I mean, the mutation-positive — we give them a TKI and then have the surgery. DR LOVE: It’s so interesting that you say that, because I have asked, I mean, 20 US lung cancer investigators. They talk about the study — I forget which one it is — where they are going to test that. They’re going to find patients with EGFR and ALK and randomly either give them prechemoradiation targeted therapy or not. And I always say, “Yes. That makes total sense. Do you do it in your practice?” And they usually say, “No. I only do it in the” — but, I mean, as you say, you’re going to make the chemoradiation first of all less toxic, I would assume. DR MOK: Absolutely. Now, as I stated, I mean, the ability to do a trial is very limited. I mean, the number of patients are so small with a Stage III mutation-positive, that right now there is 1 study ongoing in China, 1 ongoing in Korea. I think there’s 1 in the United States. DR LOVE: Yes. DR MOK: But they are not a Phase III study. Even though those that come out, they just give you some evidence that it may work, but it does not really change the practice. So I just have to adopt a little bit of common sense if I am not doing any harm to the patient. And then the chance of it responding is so high, I think it’s reasonable. And, in fact, I do have a number of these patients that finally get resection. And after resection, I give them chemo/RT as well. DR LOVE: Wow! Interesting. Before you go on with the case, since we got off on that, I guess I’m going to have to ask you: Do you use adjuvant TKIs or ALK? DR MOK: Not really, because that already got data that did not show the survival benefit. Then I cannot go against the existing data that’s negative. However, in a situation when you don’t have the data, then you can exercise your common sense a bit. DR LOVE: What data would you consider negative? DR MOK: I’m talking about the RADIANT study. I mean, that’s basically one of the largest collections of patients at this moment, which is the RADIANT study, is that selection initially by FISH or IHC. But then in a subgroup analysis, about over 167 patients that are EGFR mutation-positive, then there’s no difference in terms of overall survival between the erlotinib and the placebo. And then, however, there’s some difference in the disease-free survival, and the curves separated but statistically was still not considered to be significant. That was presented in ASCO the year before and then actually already published it in JCO. DR LOVE: Interesting. And again, I think most investigators are having the same approach as you do, although I also just learned that the big study in the US, the ALCHEMIST study that’s going to look at adjuvant therapy, both ALK and EGFR — maybe others in the future — I was stunned to see that they’ve now added a third arm, a randomization of adjuvant checkpoint inhibitor or not. Did you know that? DR MOK: I didn’t know about that. DR LOVE: I didn’t either. DR MOK: But I think the ALCHEMIST is a great effort. I have high hopes of the result of the EGFR mutation-positive subgroup, because that is the only one study using overall survival as primary endpoint and powered for such. But I’m not too optimistic about ALK, though, because the accrual is so slow. And then the chance of being in a reasonable timeframe to accrue sufficient patients is actually going to be challenging. DR LOVE: But what I’m saying is, for a doc in practice to get a patient in that study, I mean, the thing that would be interesting would be the — I know there are a lot of adjuvant trials of checkpoint inhibitors. But to be able to get into that, to me, if I’m a patient, I’d love to do that. DR MOK: Certainly. I think, especially if they offer the free genomic testing as well. DR LOVE: Yes. Great trial. DR MOK: Yes. DR LOVE: Anyhow, getting back to your case. So you had a wild-type case, so to speak, without mutations. This patient presents with this Stage IIIA disease. What did you do? DR MOK: So for this patient, actually, I decided to give neoadjuvant pemetrexed and carboplatin. And the patient did respond well. And after that, then I gave concurrent chemo/RT. Now, one of the reasons why we do that is actually a couple of reasons. One is a very practical reason, is the fact that, in Asia, sometimes to get a patient into radiotherapy, it takes time — because of waiting lists and stuff like that. And while the patient is waiting, you may as well do some treatment. So that’s one practical reason why I do that. And second is that I can actually minimize the radiation field as well. So this day, we can IMRT. We can have tomotherapy. If we can nail down the field, the chance of having a severe so-called pneumonitis is actually lower, relatively speaking. And so those are the 2 reasons why I gave the patient neoadjuvant chemotherapy. DR LOVE: So this patient got the chemoradiation therapy. And then I see you actually brought up to him the possibility of having surgery. Can you talk about that and what his reaction was to it? DR MOK: Right. So as I stated, this was generally a good-condition patient and relatively young. So whether surgery after concurrent chemo/RT is actually debatable. Now, the Kathy Albain study, that demonstrated the fact that if the patient did not require pneumonectomy, potentially there is a small overall survival benefit. Only if the patient requires pneumonectomy there is actually a detrimental effect. So for good condition, younger patients, I do actually usually discuss this possibility. I cannot say that it is actually outrageously different in term of outcome, but certainly for some patients, psychologically, they do need to say, “Oh. If I can be operated, I may have a better chance of cure.” DR LOVE: This patient was a smoker? DR MOK: Ex-smoker, yes. DR LOVE: But generally in good condition, younger patient? DR MOK: Yes. DR LOVE: If you could have gotten the patient in for chemoradiation immediately, would you still have done neoadjuvant? DR MOK: Possibly. I think either approach is acceptable to me. If the patient is ready to go and then the machine’s ready, that’s okay with me. |