New Biological Insights and Recent Therapeutic Advances in the Management of Lung Cancer: A Clinical Investigator Think Tank
Organ function and performance status to identify elderly patients who can tolerate chemotherapy
6:55 minutes.
TRANSCRIPTION:
DR LOVE: So that brings up a couple of points. And one, Corey, that Anne has as part of this write-up is, do you have an age threshold to treat with chemo? So she was 81. How about 91? DR LANGER: Done it. DR LOVE: Is there an age threshold where you wouldn’t do it? What’s the oldest patient you’ve given chemo? DR LANGER: A performance status threshold. So the oldest person I’ve ever treated, I don’t know if Watson would have let me do this, was 94, but excellent shape. You could argue what’s the point? The patient wanted treatment and did not want to be remanded to some automatic palliative approach, which frankly that patient’s pulmonologist had attempted to do. DR LOVE: It’s interesting, Dave, too. This comes up in all our programs, every single tumor type, the 85-, the 90- and the 95-year-old. But when you’re looking at a short-term, really poor prognosis, and you look at the natural history, the longevity of a 90-year-old person who’s otherwise healthy, a lot of them do survive 5 years. And they’re going to die of their lung cancer. Do you agree with this concept of just looking at performance status? I mean, would you give chemo to a person over age 90? DR CARBONE: So organ function and performance status, I think, is really the driver here. There are new tests, actually, for elderly patients’ performance that are maybe a little more quantitative than performance status. I just heard a presentation where they just tested the patient’s ability, how long it took them to stand up from a chair and walk 10 feet. Very simple. And that was far better correlated with their outcomes to therapy than a physician assessment of performance status, just talking to the patient. So I think it is not a good idea to use age alone, but some metric of performance. DR LANGER: So my in-office test is, can they get on the exam table on their own? If they can do that, no matter what my fellows told me the performance status is, that’s usually an indicator that they probably can get specific treatment. And there are very comprehensive tests on the CGS and other metrics, many of which are incredibly cumbersome. There are adapted approaches where you use just a set number of questions and performance activities to do a comprehensive geriatric assessment. Obviously we need simpler instruments, something that can be done quickly and accurately and very predictively. But I’m a big proponent of echoing Dave’s thought, that performance status and organ function really are the main determinants. DR KRIS: Yes. A quick comment. The timed get-up-and-go is a hugely predictive and easy-to-do test and underutilized. The other thing you can do is you can do it on repeated exams so you can get some kind of idea. Mrs Jones is not doing well today. You do it again, and you see that there’s a deterioration or not. It’s really, really helpful and just takes a few seconds. I fully agree with the comments before. There is no age that is predictive, except there probably is one, and that is cisplatin. I think over the age of 70, it is a really very, very special person who can take cisplatin. So I think whenever I see that, I think very, very hard about whether or not it’s doable. Let’s be honest. It is one of our toughest drugs. The core problems of it are very hard to palliate, just feeling lousy, feeling tired. And it does hit harder. If you look at all the literature about side effects of chemotherapy in the elderly, everything is a little worse. I mean, nothing is 100% predictive, but everything is a little worse. Corey, you would — DR LANGER: Oh, absolutely. DR KRIS: But cisplatin I’d be careful about. And what I do then is just, as if somebody had hearing loss or renal function, I go on the best drug I could possibly give, or combination, with that restriction, just kind of using that as another characteristic that would make me not choose a drug, like neuropathy or whatever. DR LOVE: What about single-agent or a doublet, Corey? There are trials out there looking at that in the elderly. DR LANGER: So probably the definitive trial that really has informed our approach is the Quoix effort, which compared monthly carbo with weekly taxane, in this case paclitaxel, to single-agent de jour. It was either vinorelbine or gemcitabine, either of which were equivalent. And certainly vinorelbine previously had been better than best supportive care. And that trial showed about a 4-month improvement in median survival, about a 20% improvement in 1-year survival rates, acceptable toxicity certainly by Western standards, and this included individuals between the ages of 70 and 90, including PS2. And when you look at the forest plots, the survival benefits were seen for both the young old, 70 to 80, and then the older old, 80 to 90, as well as both performance status groups. DR LOVE: What about the issue of bev in the older patient? We’ve seen some data looking at that. And did you think about bev with her? DR TSAO: Never. No. DR LOVE: Just because of her age? DR TSAO: Because of her age, actually. DR LOVE: What do you think about that thought? DR LANGER: So we did a secondary analysis of 4599, which, of course, is the trial that got bev approved. And you take that with all the usual caveats, because it was post hoc, but in that population, although you did see a response benefit, the PFS benefit went away. There was no obvious survival benefit. Again, it’s small numbers. It probably wouldn’t have been statistically significant given the trends. We’ve done a subsequent analysis, and again, lots of caveats, because it’s combining 2 separate trials where we compared the control arm of 4599 to paclitaxel/carbo/bev in both the PointBreak and the original 4599. And if you invest any face in those data, 75 may be the new 70. Above 75, bev actually seemed to have a deleterious effect. Survival was about 2 or 3 months less. Below 75, it pretty much matched anything you saw below 70, below 65. Again, 2 separate trials but essentially identical entry criteria and identical regimens. DR LOVE: I guess one thing it seemed like — I mean, I know there’s limitations to the data, but it seemed like there wasn’t that much excess toxicity, at least going up to the age of 75. Is that your take? DR LANGER: Over 75 there is. DR LOVE: But up to 75 not that much? DR LANGER: There was fourfold increase in Grade 5 events, for whatever reason. I mean, not necessarily treatment related, although most were. Below 75, there was not. |