Efficacy vs Reality: Do Time Toxicity, Quality of Life, and Cost Tip the Frontline Decision? (Round 2)

Drs Lopes and Rodriguez debate the real-world trade-offs of frontline regimens, including time toxicity, quality of life, and cost of care.

To hear arguments related to the pivotal data supporting frontline EGFR+ mNSCLC therapies — osimertinib- vs amivantamab-based regimens, see Round 1.

To hear arguments related to the impact of frontline EGFR+ mNSCLC treatment selection on subsequent available therapies — osimertinib- vs amivantamab-based regimens, see Round 3.

Transcript

Dr Santos Castillero: Round two. Rule in oncology. Number one, in my opinion, the opinion of many: efficacy, toxicity, cost. So efficacy, both regimens looks pretty much excellent, similar so far. So round two, so a little to talk about that toxicity. Because we are making our patient to live longer, this is important because toxicity is not what you show on the clinical trials and your report how that affect living and the patient performance and the function of the patient socially speaking with the family, with friends, et cetera, quality of life. So this is very important. Plus the financial consideration. 

So Dr Lopes, you start first again. What toxicity trade-off exists for your regimen and how does that impact real-world utilization? FLAURA2. All right. Focus on toxicity. 

Dr Lopes: All right. So we're back here. And again, the type of toxicity that we do see by adding platinum and pemetrexed is something that we have been used to using for quite some time. When we do look at formal quality of life assessment, we do see that you can have some adverse events that without a doubt impact patient's quality of life and their day-to-day lives. But we have to remember that these patients also are away from having worsening lung cancer symptoms for longer. So that kind of balances and it's a trade-off that most patients are willing to do. And again, we often discuss carboplatin pemetrexed as not being your aunt's chemotherapy. This is not breast cancer chemotherapy. This is not a regimen that most patients feel very bad with. 

Having said that, there are patients who have severe, especially fatigue, and there have been many patients who have had to stop therapy because of edema that often becomes refractory to even using diuretics. So it's not a completely benign regimen, no chemotherapy is. But as the regimens we have, it is pretty decent. And as regimens we have in lung cancer, it's actually been the easiest to use for the longest. And that's why we had data before the targeted agent era, showing that if we use maintenance pemetrexed, patients actually do live longer with acceptable quality of life. And we were never able to show that with a taxane or even gemcitabine. So without a doubt, there is a role. But of course, there is a trade-off with symptoms, always reminding that the lung cancer symptoms are controlled longer. 

There's a few caveats, and I don't think we have ... We do have the renal damage one here. So we usually would not use pemetrexed in anybody with the GFR glomerular filtration rate of less than 45. There are some studies that suggest some strategies that you can use, but as a general rule, we do not use it in patients with lower GFR. 

And of course, we have the usual adverse events that we can see. Patients still need to come to get hemo every three weeks. They will get carboplatin for usually four cycles. Sometimes we do extend it to six, although that has become rarer and rarer. Occasionally, we can have QTC interval changes with the combination regimen, anemia, myelosuppression, but those are usually quite manageable as long as patients are getting folic acid and vitamin B12 and folic acid daily and the vitamin B12 every three cycles or nine weeks or so. 

We actually even saw some clinical trials trying to give a dose of 1,000 milligrams of pemetrexed per meter square. And the toxicity in those trials, as long as patients were compliant with their folic acid and vitamin B12 was actually not that much different than 500. So it is a very well tolerated regimen. And we can certainly discuss how long we continue pemetrexed these days because there's interesting numbers to discuss. 

When we look at cost, this is the total first-year cost for osimertinib plus platinum pemetrexed for all payer $160,000, private versus Medicare, $79,000 versus $235,000. And this was a poster presented at the pharmacoconomics conference in Montreal last year. And this is your typical cost of care model. Usually our medical oncology audiences do not have a lot of interest in this. I'm just going to pass it to the next slide and ask Estela to come back on stage. 

Dr Rodriguez: Great. I don't think I'm going to win here on the cheap drug, but let's try. So toxicity trade-offs. So actually, I will commend actually J&J. They actually collected this data on PROs, Patient Reported Outcomes early on. Actually, Jill Feldman, who's a great advocate, was actually a presenter of this data. But you can tell that there is an improvement in performance status and global health status for these patients. And there's not a big difference between the ami-laz and the osimertinib. So regardless of all that toxicity and they had COVID and VTE and everything else, patients reported improvements in symptoms. 

So how do you measure the improvement and the toxicity cost? It's just the whole equation that I'm not in economics, so it's hard to do. But I will tell you that the time toxicity, there's been a lot of effort to at least make the time toxicity better for patients. And fortunately today, we have all our patients now in subQ. They can get every four-week dose after the first month. So they're really spending ... I told a patient it's five minutes, but then I didn't realize I forgot to sign the orders and they went upstairs and they have to wait for the medication to be mixed. So it's not five minutes in our clinics because things happen, but it is going to definitely be ... They're going to be out of there in an hour or half an hour if we have it all together because it's truly a subQ administration. 

Now they still have to drive to the cancer center and park the car and pay a fee. But every four weeks, it's definitely better than coming every three weeks and better than the prior amivantamab every two weeks. 

Now, the average reaction management, that also takes time from patients. I mean, I think this is one regimen that requires patients to be an active participant of the skincare. So I always don't want to assume that guys cannot do that because I know plenty of men that do wonderful job with their skincare. So I ask them, this requires antibiotics and creams and lotions for your fingers and toes. And then a lot of men get scalp and problems in their face, which is something I discuss with patients. People will be able to tell that you're on this. And we can make it better. We definitely, my nurse has asked me to be lessened to just be very clear that it will get better after a couple of months. It's not going to get better in a week. And it does get better, partly because we learn to manage it better, the patient, and we also learn to dose reduce and adjust. 

But the thromboembolism, that can be managed. The ocular toxicity is very rare. The ILD pneumonitis in both of these regimens is rare. So it's really the skin that I think ... 

Now here's where I lost, because this is the same paper looking at data and a big difference for all payers, private insurance, and even Medicare for a new drug. Now, you have to kind of talk ... In the United States, patients don't look at this data unless you're paying in the healthcare system and a politician. So patients ... I had never even seen this data myself, but I thought to myself, "Well, what does this buy patients this cost to the system?" So if you're buying extra year of life and if patients are not getting complications from chemotherapy that they'll land the hospital, that is key. 

This whole regimen also accounted for the administration and the disease management, which I think this data will be, whatever they estimated for skincare management is going to be less with all the new regimens. So they estimate will be at least 15% reduction in that management of the dermatologic costs. But nonetheless, it's definitely more expensive.