DR RIELY: This is a woman who was referred to me by one of the other oncologists at the center because he’d treated her bladder cancer 8 years before. So this was back when she was 73, she got induction gemcitabine/cisplatin for bladder cancer, underwent a resection and is NED from the perspective of bladder cancer. Was getting routine follow-up scans. And a follow-up scan for the bladder cancer showed a lung mass. Subsequently diagnosed with a Stage II lung cancer, a hilar node positive, no mediastinal nodal involvement. She underwent surgical resection and then came to see me to find out what else she should do. Molecular analysis was done on the tumor. It was actually KRAS mutant, and it was an adenocarcinoma.
DR LOVE: Okay. So Dave, 81-year-old otherwise healthy lady. You heard this history. She’s got a resected Stage II adenocarcinoma. What are you thinking about in terms of adjuvant therapy?
DR SPIGEL: A couple of things. One is that she’s had this experience already of getting diagnosed with cancer, going through therapy to cure her. And now she has another cancer and probably has the same goals, right, that she wants to do whatever she can to keep it from happening. So she clearly qualifies from a physical and medical standpoint to receive adjuvant therapy. The question is, what would you give her?
So I just want to create some controversy here, so I wouldn’t think twice. I’d give her carbo/pem. That’s what I’d give her in the adjuvant setting, knowing that the only data we have come from a small study that was in the last session of ASCO about 2 years ago, that suggested, actually, a disease-free survival advantage compared with cis/vinorelbine with a cis/pem regimen in the adjuvant setting. It was about 200 patients, and it was done in Europe, but it’s the only data we have in the adjuvant setting with a pem-based regimen. And I think everyone is familiar — although I didn’t participate in ECOG-E1505, the pivotal adjuvant trial with bevacizumab, pemetrexed was allowed to later be added as a choice of a regimen, although with cisplatin.
This gets even easier for me, because she’s already had cisplatin, so I can make an argument that I don’t want to add to any cisplatin toxicity. But I’d feel comfortable with carbo/pem with her for 4 cycles.
DR LOVE: So just out of curiosity, just to be clear, putting aside the previous history with the cis in general with adenocarcinoma in a younger patient, for example, carbo/pem?
DR SPIGEL: I think it depends what argument you use. I think we generally think that cis is a little bit more active than carbo, probably doesn’t make a difference in the advanced disease setting, where we think more about quality of life. In the early stage setting where we’re trying to get every bit out of that 5% absolute survival and cure, maybe cis is that little bit of extra difference you need.
DR LOVE: So, you’re generally going to use pem and – what? – cis in younger patients? Carbo, older?
DR SPIGEL: So – yes. That’s a fair way of saying. But I – I can’t think of a patient where I’ve used cis in the last several years in the adjuvant setting.
DR LOVE: Hmm. Interesting. That’s always – I love to hear that one out on the table. So Ram, I’ll ask you the same question: What would you be thinking about with this 81-year-old lady? And in general, how do you approach adjuvant therapy of adenocarcinoma?
DR GOVINDAN: So the first question is, should we be treating 80-year-olds for adjuvant therapy? Second, what drugs? And third, of course, this cis/carbo thing. The first is — the NCI Canada study always makes me somewhat concerned when it comes to elderly patients. The subset analysis showed there was actually an adverse outcome when we took elderly populations and then they got adjuvant therapy. In fact, the hazard ratio, if I am not mistaken, was more like 2. Bad for chemotherapy. So I actually, in general —
DR LOVE: So what would the age —
DR GOVINDAN: Eighty. Eighty and above, I thought.
DR SOCINSKI: No.
DR GOVINDAN: The subset of the 80 and above, it’s even worse.
DR SOCINSKI: Oh, yes. There were like 9 patients.
DR GOVINDAN: Yes. And elderly patients in general, that’s the concern. And so I’ve actually strayed away from the adjuvant therapy in general in 80 and above. That’s my general approach.
DR LOVE: Interesting. So Chandra, what would you be thinking about in this 81-year-old lady?
DR BELANI: I think if I have to give adjuvant therapy, I’d give cisplatin.
DR LOVE: You don’t have to.
DR BELANI: And — but I do not give it in 80 years and above, as Govindan.
DR LOVE: You don’t give adjuvant therapy period?
DR BELANI: I mean, if she’s a physiologically 70 or 75 when she presents at age 81, I could probably consider giving it.
DR SOCINSKI: I mean, the problem is, is that all the major trials we have in the adjuvant setting —
DR BELANI: Are cisplatin.
DR SOCINSKI: —are cisplatin, but the elderly, even above the age 65, were really under-represented on these trials. So we really don’t have good data. And I would have a long discussion with her about — at best, the LACE meta-analysis in Stage II disease would tell us we have a hazard ratio of 0.83. So, that’s a 17% reduction in the risk of recurrence. She has N1 disease. So if she were willing to accept what is a relatively small absolute benefit, I might do it.
DR LOVE: Do — what would you give her, specifically?
DR SOCINSKI: I would optimally give her cis/pemetrexed. However, I would be very concerned in an 81-year-old about the toxicity of cis. I’ve always felt, since we don’t have clear data in the adjuvant setting, and I teach our fellows this: If you think you have to give carbo, maybe you shouldn’t be doing it.
DR LOVE: Ram?
DR GOVINDAN: So I want to underscore one important point. Pemetrexed causes renal toxicities, more than people appreciate.
DR SOCINSKI: Yes.
DR GOVINDAN: In fact, it drops the creatinine clearance. You can see that actually happening. In an 80-year-old with as it is a physiologically decreased renal function, giving the 2 drugs…If I have to give adjuvant therapy, I would use, as David said, a carboplatin-containing regimen, even though we don’t have a whole amount of data. I would at least minimize the bad outcomes. And my preference would be to give pemetrexed and carboplatin. If I have to.
DR LOVE: Let’s do a quick poll here in terms of your usual adjuvant recommendation in a younger patient with adenocarcinoma, 60 years old. What are you most likely to recommend?
DR SOCINSKI: Cis/pem for the nonsquamous and I give them a choice of cis/docetaxel or cis/gemcitabine for the squams based on side effects.
DR RIELY: Cisplatin/vinorelbine.
DR GOVINDAN: Cis/vinorelbine for squamous. Cis/pemetrexed for nonsquamous.
DR SPIGEL: Carbo/pem for the nonsquamous and carbo/paclitaxel for squamous.
DR BELANI: Cis/pem for nonsquamous and cis/docetaxel for squamous.
DR HEYMACH: Yes, it’s the same, cis/pem and cis/docetaxel. We did a neoadjuvant study with cis/docetaxel, and the response rates were upwards of 60% in the neoadjuvant setting. So I think for nonsquamous, that’s a highly active regimen.
DR LOVE: So what happened with this lady?
DR RIELY: So I’ll preface this by saying I am the world’s worst salesman for adjuvant chemotherapy. I walk in there and say, “This is barely better than doing anything. This is something that you’re here to talk about, what you can do, and this is what we’ve got.”
DR HEYMACH: How could they not jump at that?
DR LOVE: And how often do people in their sixties say, “Okay. I don’t think I want any”?
DR RIELY: I get about 20% to 30% of people who say, “No thanks.”
DR SPIGEL: Depends how surgery went.
DR BELANI: One out of 4 say no.
DR SPIGEL: If they’re struggling with surgery complications.
DR LOVE: But he sounds like he’s presenting it in a lot more negative light than most people do. But what did she decided to do?
DR RIELY: So she said, “I would like chemotherapy.” And I gave her cisplatin/vinorelbine. And it wasn’t a smooth course, but she got about two thirds of dose in.
DR LOVE: And what’s her status right now?
DR RIELY: She’s had recurrent disease. She recurred about 10 months after completion of adjuvant chemotherapy.
DR LOVE: And can you talk a little bit more about the tolerability that she experienced in terms of the cis/pem? I’m sorry, the cis/vinorelbine? What exactly happened?
DR RIELY: So she had some difficulty with myelosuppression, as most people do with that regimen. Fatigue was probably the biggest complaint she had. Surprisingly, her renal function actually did just fine during all of it, perhaps because she had to hold dose because of myelosuppression from time to time. But fatigue and myelosuppression were really the key things.