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Most of what I write about here highlights the evidence supporting treatments, and that’s certainly how we strive to practice oncology. But the reality is that patients and doctors often find themselves in the middle of settings where we don’t have any answers and need to rely on judgment, or we think we can potentially do better by defying conventional wisdom. Doctors lie all along the spectrum of being “data-driven” on one end and being a “cowboy” on the other end. The general perception is that many academics are more evidence-based, but I’m not sure that’s true: experts defy the guidelines all the time and say that the key is knowing when to follow and when to deviate from them.
One of the typical places in which we find ourselves at odds with a lack of evidence is in treating patients beyond about third line treatment. We have trials that show the evidence of a limited number of our treatments for NSCLC out to third line, and second line for SCLC. Most patients run out of energy and/or interest in treatment by about that time, but some patients have slow-growing and/or particularly responsive cancers and come back after multiple lines of treatment feeling well enough to come back to the clinic and ask, “what next?” Many people participating here are beyond the point where we have evidence that further treatment is beneficial. How do we manage these situations?
The short answer is that it’s completely individualized, a product of the patient and the doctor, so I can only offer my perspective. I generally consider myself on the more data-driven and analytical side, which isn’t to say that this is better or worse than being a renegade. In my group of 10 oncologists, I think I’m in the middle to conservative side, with a couple of partners who consistently treat far, far beyond where the evidence lies, and many of their patients adore them for this. Offering another and another and another line of treatment brings with it some renewed hope, a precious commodity in oncology. Sometimes I think it’s far easier to continue treatment, even when we are nearly certain it will be futile. Having a hard conversation about switching to comfort care is often uncomfortable, and some patients and caregivers can feel betrayed or given up on. Our treatments run an increasing risk of becoming harmful, with treatment less likely to be tolerated well, compared with (usually) a smaller and smaller chance of responding well as the cancer becomes more resistant. And there is also the very real concern that pushing on with aggressive treatment and deferring on considering the challenging reality of future decline will keep patients from receiving the focus on comfort that could help them more, and could keep people from facing the practical preparations of what lies ahead.
Though I do consider myself relatively conservative in my medical practice style, a significant minority of my patients receive fourth line or later treatment for NSCLC, some going on with treatment after treatment for years, and far beyond where the evidence for benefit ends. Although I’ve heard several professors and large numbers of general oncologists say that they never give more than three lines of treatment, which would make me feel that I’m far out of step with my colleagues ("Jack West" does sound like a good name for a cowboy), I have also seen many patients who travel from expert to expert around the country over years, collecting ideas along with treatments. Seeing how many of my fellow experts have administered 6th line treatment, I’m pretty confident that there’s no real optimal answer.
My approach is to primarily use the performance status of the patient, combined with the responsiveness of their tumor, to guide my discussions with a patient. It’s only a minority who are still feeling well after three or four lines of treatment, but if they are minimally symptomatic, and particularly if they have responded well to prior treatments, I think it’s quite reasonable to explain that the remaining options you might consider don’t have compelling evidence to back them but are something to think about. The turning point for me is when I believe that further treatment is clearly more likely to be harmful than helpful to that person. Over time and ongoing treatments, a patient typically becomes weaker and their cancer becomes more resistant, so the likely benefit declines. Moreover, you need a certain threshold of strength to tolerate the rigors of cancer treatment, and people below that are likely to be dragged down by further chemo or a targeted therapy (which, though not called chemo, just have different side effects, rather than no side effects).
There is no perfect doctor for every patient, and sometimes we reach a point where I am uncomfortable offering more treatment to a patient who wants more despite my best judgment. There’s certainly some give and take, but sometimes patients will seek out other opinions and find another oncologist who is more inclined to continue to treat them. While I think that an oncologist’s goal should be to serve a patient’s needs, it’s a troubling, gray area if they feel they are being asked to offer harmful therapies.
Fortunately, that disconnect is pretty uncommon, since more often than not, I and my patients come to understand each other over our time working together. But these issues are always difficult waters to navigate. Having the comfort of a straightforward standard is easy. Determining what to do when there is no information to go on, or what you know seems like an unappealing alternative, is hard.
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Hi elysianfields and welcome to Grace. I'm sorry to hear about your father's progression.
Unfortunately, lepto remains a difficult area to treat. Recently FDA approved the combo Lazertinib and Amivantamab...
Hello Janine, thank you for your reply.
Do you happen to know whether it's common practice or if it's worth taking lazertinib without amivantamab? From all the articles I've come across...
Hi elysianfields,
That's not a question we can answer. It depends on the individual's health. I've linked the study comparing intravenous vs. IV infusions of the doublet lazertinib and amivantamab...
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