This transcript has been edited for clarity.
Hello, this is Mark Kris, from Memorial Sloan Kettering, speaking to you today about my experience at a recent meeting of thoracic medical oncologists during the IASLC 2025 Targeted Therapies of Lung Cancer Meeting in Huntington Beach, California.
If I could set a theme for that meeting, it would be: It's complicated. The speakers [reiterated] that, with so many more choices and targets, choosing the best therapy for a patient is becoming much more difficult.
However, because we have more ways of fighting these cancers, we have a better chance of helping patients. I think you've heard me say before, “Better for patients, tougher for oncologists.” That's okay. That's what we signed up for.
I'd like to talk about the different stages of lung cancer and start with metastatic cancer. What is the initial treatment? As the meeting went on, it became tough to make any generalizations there. I'd like to make a couple, and we'll see if you agree, but I think this is a reasonable way to move forward.
For targets with a high likelihood of benefit and excellent tolerability — such as EGFR, ALK, ROS1, RET, and NTRK — when you find them in the face of metastatic lung cancer, I think there's general agreement that you would start with a targeted therapy. Response rates for all these [are] in excess of 75%, and tolerability is decent.
The issue comes, however, for the duration of therapy. I think the sad conclusion from all these drugs is that, no matter how good they are, absolutely none are curative. What do we do? What can we add?
We don't have much here, but one piece of data we do have comes with EGFR. If you add a standard chemotherapy, and we have randomized clinical trial data for this, you can improve the duration of response and the progression-free survival.
Many folks have said that this may not be the most appropriate endpoint, but I really would like to challenge that, and I'd like to do so on several levels. The first is that the recurrence of the cancer is absolutely devastating to the person with the cancer. People have so many negative thoughts at the diagnosis, and then after receiving agents like osimertinib or lorlatinib that give a great response and are very tolerable, you're taken off that very negative feeling.
When it comes back, though, all those negative feelings return. Every recurrence and progression is absolutely devastating to a patient. It reinforces in a very strong way that they have a deadly cancer. Preventing recurrence and delaying recurrence is very important.
Second, we cannot predict what the nature of that recurrence might be. It might be a brain metastasis. Even with osimertinib, roughly 15% of people have a new cancer in their brain. Even if you can control it, it is devastating. You can't predict what it might be, [whether] it’s a painful bone metastasis, or whatever [else].
Third, you can't guarantee benefit from the next therapy. What are the next therapies? Again, I'll focus on EGFR. By giving chemotherapy after progression on osimertinib, randomized trial data show the progression-free survival is about 6 months and the overall survival is about 15 months.
Saving that therapy for very short progression-free survival — very short survival, I would say — just doesn't make sense to me. I would think that chemotherapy should be part of the standard therapy for every patient who is receiving targeted therapy and is very likely to benefit.
Again, I think we have strong data with osimertinib and chemotherapy: others, less so. I ask you to think about it and think about it in the context of each patient. Could the drugs be given safely? Is it something that goes along with the patient's wishes? I think it makes sense to have it on the table with each patient, particularly with EGFR where the data are there.
I know there's disagreement in the oncology community, but I think for the reasons I’ve said — the devastating effect on the patient, the inability to actually predict response, to predict the kind of [benefit] and the short benefit with the second-line therapies, and the inability to say what the nature of that progression will be — we need to do all we can to try to prevent it.
In the subsequent talks, I'll be speaking about other targeted therapies in the initial setting and whether you start with them or standard.
COMMENTARY
It’s Complicated: Navigating Targeted Therapies for Lung Cancer
DISCLOSURES
| April 11, 2025This transcript has been edited for clarity.
Hello, this is Mark Kris, from Memorial Sloan Kettering, speaking to you today about my experience at a recent meeting of thoracic medical oncologists during the IASLC 2025 Targeted Therapies of Lung Cancer Meeting in Huntington Beach, California.
If I could set a theme for that meeting, it would be: It's complicated. The speakers [reiterated] that, with so many more choices and targets, choosing the best therapy for a patient is becoming much more difficult.
However, because we have more ways of fighting these cancers, we have a better chance of helping patients. I think you've heard me say before, “Better for patients, tougher for oncologists.” That's okay. That's what we signed up for.
I'd like to talk about the different stages of lung cancer and start with metastatic cancer. What is the initial treatment? As the meeting went on, it became tough to make any generalizations there. I'd like to make a couple, and we'll see if you agree, but I think this is a reasonable way to move forward.
For targets with a high likelihood of benefit and excellent tolerability — such as EGFR, ALK, ROS1, RET, and NTRK — when you find them in the face of metastatic lung cancer, I think there's general agreement that you would start with a targeted therapy. Response rates for all these [are] in excess of 75%, and tolerability is decent.
The issue comes, however, for the duration of therapy. I think the sad conclusion from all these drugs is that, no matter how good they are, absolutely none are curative. What do we do? What can we add?
We don't have much here, but one piece of data we do have comes with EGFR. If you add a standard chemotherapy, and we have randomized clinical trial data for this, you can improve the duration of response and the progression-free survival.
Many folks have said that this may not be the most appropriate endpoint, but I really would like to challenge that, and I'd like to do so on several levels. The first is that the recurrence of the cancer is absolutely devastating to the person with the cancer. People have so many negative thoughts at the diagnosis, and then after receiving agents like osimertinib or lorlatinib that give a great response and are very tolerable, you're taken off that very negative feeling.
When it comes back, though, all those negative feelings return. Every recurrence and progression is absolutely devastating to a patient. It reinforces in a very strong way that they have a deadly cancer. Preventing recurrence and delaying recurrence is very important.
Second, we cannot predict what the nature of that recurrence might be. It might be a brain metastasis. Even with osimertinib, roughly 15% of people have a new cancer in their brain. Even if you can control it, it is devastating. You can't predict what it might be, [whether] it’s a painful bone metastasis, or whatever [else].
Third, you can't guarantee benefit from the next therapy. What are the next therapies? Again, I'll focus on EGFR. By giving chemotherapy after progression on osimertinib, randomized trial data show the progression-free survival is about 6 months and the overall survival is about 15 months.
Saving that therapy for very short progression-free survival — very short survival, I would say — just doesn't make sense to me. I would think that chemotherapy should be part of the standard therapy for every patient who is receiving targeted therapy and is very likely to benefit.
Again, I think we have strong data with osimertinib and chemotherapy: others, less so. I ask you to think about it and think about it in the context of each patient. Could the drugs be given safely? Is it something that goes along with the patient's wishes? I think it makes sense to have it on the table with each patient, particularly with EGFR where the data are there.
I know there's disagreement in the oncology community, but I think for the reasons I’ve said — the devastating effect on the patient, the inability to actually predict response, to predict the kind of [benefit] and the short benefit with the second-line therapies, and the inability to say what the nature of that progression will be — we need to do all we can to try to prevent it.
In the subsequent talks, I'll be speaking about other targeted therapies in the initial setting and whether you start with them or standard.
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
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