Lung Cancer / Mesothelioma
(1 votes, average: 5 out of 5)
Loading ...As I described in a recent post introducing the concept of the series, “What I really do”, I wanted to provide a summary of how interpret the evidence I show here, how I really approach real life patients. Some of this will illustrate that the experts don’t agree 100%, and that we all add some interpretation and style to how we manage patients. What I describe isn’t meant to be a dogmatic declaration of what everyone should do, but just the way I apply the evidence from trials of somewhat selected patients in the real world. At the same time, I typically modify plans based on things like a patient’s other medical problems, their aggressiveness vs. aversion to side effects, travel distance to get to me, and other factors. I don’t have any setting where 90% of patients get the same treatment, because I think many patients need a more individualized approach.
That said, let’s start on how I think about a patient presenting with new advanced NSCLC, which is the stage at which about half of the patients with NSCLC are diagnosed, and a higher proportion of my lung cancer patients (because many of the patients with early stage NSCLC, especially stage I, may not need or be feasible candidates for chemo).
Performance status is the first indicator. There’s certainly some correlation with age, but most experts agree that the overall activity level of the patient counts far more than chronologic age. A 77 year old man who walks his dogs 2 miles per days is a much stronger candidate for aggressive treatment than a 57 year old with severe emphysema who rarely leaves the house because she becomes short of breath making the bed or walking around. Treating poorer risk patients is a separate issue, so we’ll concentrate on healthier patients who are able to manage their own activities of daily living (ADLs) without assistance and get out and about.
Within the healthier population with advanced NSCLC, the question I ask is whether they are a candidate for avastin (bevacizumab), which has been shown to improve survival for a limited subset of patients who don’t have brain metastases, squamous NSCLC, active heart disease, require full dose blood thinners, or have a history of coughing up blood (prior post here). Since that initial approval of avastin for lung cancer, increasing evidence has emerged suggesting that it’s probably pretty safe to give avastin to patients with treated brain metastases (prior post here), and also for patients on blood thinners (prior post here), but right now the FDA approval doesn’t include these groups, and serious or even fatal bleeding episodes can occur even in well-selected patients receiving the treatment, Avastin added to carbo/taxol, just as it was given in the large trial that led to its approval. If a bleeding complication occurs in someone treated as Avastin was approved, it’s a terrible thing, but it’s known to happen. But if, God forbid, a patient on blood thinners bleeds, or someone with a treated brain metastasis has a hemorrhage in their brain, there’s no way to prove it didn’t happen because you treated someone outside of the FDA guidelines. And some people feel that even if you have a careful discussion with a patient with brain metastases or on blood thinners, and even if you document the risks well, a family member can still come back months after a patient’s unfortunate death and sue their doctor. I happen to be one of those people, so I use avastin by the book. And for the sake of completeness, I wouldn’t consider trying it in someone who has coughed up any significant amount of blood (more than slight flecks or streaking), nor someone with squamous NSCLC, since both groups continue to look like they have an unacceptable risk of bleeding complications.
So if patients are eligible and are inclined to pursue it, I recommend carbo/taxol /avastin for up to six cycles, then maintenance avastin. I don’t have a real problem with other platinum-based doublets combined with avastin, but no other regimen has shown a survival benefit, and cisplatin/gemctibine has failed to show a survival benefit in the AVAiL trial (prior post here). This trial also showed that a lower dose looked comparable to the higher dose (but neither was better than placebo). Putting it all together, I think it’s reasonable to give a lower dose, but I still favor the higher dose that was used in the ECOG trial, the only one that showed a survival benefit, particularly since the side effect profile wasn’t appreciably better with the lower dose.
Another point is that the failure of the AVAiL trial to show a survival benefit suggests to me that avastin’s benefit isn’t astounding: I would have hoped to see it significantly improve overall survival with the cisplatin/gemcitabine regimen if it were that remarkable (most oncologists have considered the regimen attached to avastin to be pretty much interchangeable, since we presumed that the effect of avastin would be the same for all of these doublets). One large trial was positive, and another was negative, and I’m not sure that we’d consider it a standard of care if the negative trial had been reported first. But as it was, US-based oncologists were already conditioned to accept avastin as part of our initial plan, and the AVAiL trial leaves enough unanswered questions that I don’t think it was enough to reverse our practice of giving it. But it didn’t increase my confidence about how much the avastin was adding. So I don’t think it’s a crucial mandate that every eligible patient receive avastin. And it’s something I think about in a patient who is perhaps borderline for eligibility, maybe because of treated stable brain mets or anticoagulation or has had some mild hemoptysis (coughing up blood). While there is growing experience suggesting that we can be more comfortable giving avastin to patients who may have previously been excluded or are just questionable for it, is it clearly beneficial enough to accept the risk if it didn’t show a benefit in both of the large trials that studied it?
The other issue is that an analysis of patient age on the ECOG trial showed that elderly patients (defined as 70 and older) didn’t receive the same degree of survival benefit and experienced a significantly higher rate of many side effects compared with younger patients (prior post here). The trial wasn’t designed to test this, and this remains a debatable point, but I definitely discuss this issue with older patients, and although I wouldn’t hesitate to recommend the triplet to a fit 72 year old, I’d think hard about how to guide a 78 year old.
That’s more than enough for now. I would estimate that only about 40% of my patients are eligible for avastin, so another post will cover how I approach healthier patients who aren’t candidates for avastin for one reason or another.
Posted in: Core Concepts, First-line treatment, Lung Cancer, Non-Small Cell Lung Cancer (NSCLC), Stage IV/Advanced/Metastatic NSCLC, What I Really Do
email to a friend
printer friendly
This is Tracy Yao from shanghai China. My father is suffering suspicion of LC. May I find an experienced doctor who can give me some directions here? I am very very very eager to get the supports from GRACE. Waiting for your feedback.(My email is tracy.baobao@163.com) Thanks a lot.
Tracy Yao
Tracy,
I sent you an e-mail as well. You would need to read some of the information in the subject archives here once you have a better idea of what you’re looking for. We can’t provide personal treatment recommendations for individual patients, since only a person’s doctor(s) should do that. We can provide some general information about lung cancer, and that’s what you’ll find here.
-Dr. West
Dr. West,
As per usual, I’m always interested in knowing how a particular chemo regimen might work on bone mets. Does the Carbo/Taxol/Avastin regimen followed by an Avastin maintenance work well in that scenario? Or, would you choose a different regimen for someone who presented with bone mets, but otherwise meeting the criteria for the described triplet? If used, have you any sense of how well the Avastin maintenance halts bone met progression? Btw, as you probably know, we don’t normally have access to Avastin for NSCLC in Canada, except in a trial setting, but it’s interesting to hear how it would be used.
- bev
Dr. West:
I understand that you prefer carbo/taxol/avastin as your standard first chemo regime. If the patient is fit, isn’t there a small statistical advantage (in terms of Overall Survival) when one uses cisplatin instead of carboplatin?
Also, how confortable will you be to use carbo/alimta as first line for a patient with adenocarcinoma?
And finally, if the patient has adeno with bac features, will you be incline to change the combo carbo/taxol/avastin to something else for the first line?
Thanks much!
Carlos
carlos
Bev,
To my knowledge, there’s really no evidence and no sense at all that any one regimen for advanced NSCLC works better for bone mets than another. Similar to the way we highlight the difference between a lung cancer metastatic to the liver and a “liver cancer” (primary liver cancer” that started there, the cell of origin is the key. So we don’t distinguish between lung cancer metastatic to liver or adrenal and lung cancer metastatic to bone, and that doesn’t factor in at all for me. I think it’s possible that in many years we’ll sift out those relationships, but we’re only emerging from the dark ages of treating all NSCLC the same, now recognizing that the different histologies are potentially worthy of treating differently. And I actually suspect that the next step will be profiling based on gene signatures, tailoring therapy based on the molecular characteristics of the biopsied cancer rather than by a pattern of where it has spread.
Carlos,
You’re right that there is a small statistical advantage to cisplatin-based chemo over carbo, but that’s outside of the setting of combining with avastin. So far, the only evidence we have for a survival benefit with avastin is when it’s paired with carbo/taxol, and the only well-studied cisplatin-based regimen, cis/gemcitabine, didn’t show a survival advantage for the chemo/avastin combination. So while I’d consider cisplatin combinations for avastin ineligible patients (though I still don’t recommend it for the majority of patients, largely because of concerns about the balance of activity vs. side effects, and I also think that the benefit of cisplatin almost certainly gets washed out in patients who receive two or three or more lines of therapy), I don’t see a clear role for regimens other than carbo/taxol with avastin for lung cancer just yet.
Now, the regimen of carbo/alimta has also been tested in an approximately 80 patients trial, in which avastin-eligible patients (all non-squamous by definition, for eligibility to receive avastin, so obviating concern about lower activity of alimta in patients with squamous cancers) received carbo/alimta/avastin for 6 cycles, after which non-progressing patients received a combination of ongoing alimta and avastin. This study, by Dr. Jyoti Patel at Northwestern, didn’t show serious safety concerns, and the survival appeared favorable. I’d consider it to certainly be an option, but my preference is to give avastin the way it was done in the positive trial and not take liberties, both out of concern for riks of unappreciated side effects and for the fact that an alternative chemo regimen didn’t show a survival benefit as an avastin combination. Personally, I have no great love for carbo/taxol as a combination, but I also think that the platinum-doublets are so similar overall that I don’t see a reason NOT to use the one that has the best evidence in its favor here.
Finally, I’ll cover the platinum/alimta combination without avastin as a first line option in an upcoming post about avastin-ineligible patients. The short answer is taht I struggle with it. I think that the cisplatin/alimta regimen looked very good for non-squamous patients, but cisplatin isn’t for everyone, and we can’t presume that carbo/alimta is just as good (a phase III trial of carbo/alimta vs. carbo/gem showed a median overall survival that was rather unimpressive, at a little over 7 months for both arms. It’s not fair to compare results across trials, since the patients and overall care received may have been a little different for the two trial settings, but you can’t presume that carbo/alimta is going to give an 11-12 month median survival. However, it appears to be every bit as good as anything else out there for non-squamous NSCLC patients, and it’s usually very, very well tolerated (in the carbo/alimta vs. carbo/gem trial, the efficacy was the same but side effects were fewer with carbo/alimta). My leading hesitation with using alimta up front is that I like it a lot as a second or third line agent, and you lose that if someone progresses after a few cycles of carbo/alimta or the same with avastin. But I think that it’s completely fine, and it could potentially lead into maintenance alimta or alimta/avastin after 4-6 cycles of the doublet initially.
I’ll cover BAC as a separate post in the next week or so. I don’t think there’s enough true data to say anything definitive, but I’ll cover my impressions in an upcoming post.
-Dr. West
Posts
| Core Concepts
| Subject Archives
| Monthly Archives
| Resources
| 
Donate
| Forums
| GRACE Home
Disclaimer: The information provided at GRACE is for informational purposes only. The faculty of GRACE is not providing medical advice, diagnosis or treatment and cannot replace the medical advice of your doctor or health care provider. (Full Disclaimer)
© 2007-2008 GRACE. All rights reserved.
5 Comments
Login (Must Be Logged In To Comment)