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Various Forms of Disease Progression in Advanced NSCLC

Panelists: Mark A. Socinski, MD, Florida Hospital Cancer Institute; Maximilian Hochmair, MD, Otto Wagner Spital; Suresh Senan, MRCP, FRCR, PhD, VU University Medical Center; Leora Horn, MD, MSc, FRCPC, Vanderbilt University Medical Center; Thomas E. Stinchcombe, MD, Duke University Health System
Published: Wednesday, Dec 05, 2018



Transcript: 

Maximilian Hochmair, MD: We were talking about pseudoprogression in the beginning of treatment. It does not occur as often as we thought; it’s about 3% to 5% of our patients when we collected data. The decision is always important if there’s a progression; we should switch to chemotherapy. When we do the combination then, it’s not that clinically relevant. From my point of view, the pseudoprogression will happen in the beginning, but in the longer period I did not see pseudoprogression. After half a year and we see progression, it’s real progression and not pseudoprogression.

Mark A. Socinski, MD: I agree. We are oversold on pseudoprogression in lung cancer. The issue that I wanted to get your opinion on is hyperprogression, which is real. Around 5% of the patient population may have hyperprogression. We struggle with what the true definition is, but we know it’s real in clinical practice. What are your thoughts?

Maximilian Hochmair, MD: We had a poster at the European Society of Medical Oncology [ESMO] 2018 annual meeting about this fact that we can measure it with biomarkers—CTL4 [cytotoxic T-lymphocyte-associated protein 4] cells. It’s a clinical and relevant issue because we have to be able to identify pseudo- from hyperprogression. In my clinic, those patients sometimes run away fast and you cannot stop them.

Mark A. Socinski, MD: We don’t understand the mechanisms of resistance to immunotherapy [I-O] agents. It’s different if you have a patient who’s maybe been on I-O for 18 months and then progresses. That’s different obviously from the other end of the spectrum where you progress in the first 6 weeks. I don’t know that we understand the biologic differences from those sorts of things. There is some data, getting back to docetaxel [Taxotere] and ramucirumab [Cyramza], from an unplanned retrospective analysis on how rapidly you progress after first-line treatment. There was some evidence that if you transition to second-line therapy treatment, there was activity with docetaxel/ramucirumab in that population. Thoughts about this?

Maximilian Hochmair, MD: In the nintedanib [OFEV] data in the LUME-Lung 1 trial we saw the same thing. When the patients progressed in the first 6 months, the antiangiogenic drug worked much better. For those patients who are fast progressing, they need ramucirumab or nintedanib.

Mark A. Socinski, MD: That’s the take-home message: for patients who progress quickly, there’s still an option from which they may benefit. It probably is the combination of docetaxel with an antiangiogenic agent in that setting.

Leora Horn, MD, MSc, FRCPC: Although, the one thing to consider is the patients with hyperprogression benefit more from a single agent than combination therapies.

Mark A. Socinski, MD: Yes.

Leora Horn, MD, MSc, FRCPC: If they progress on a single agent, they should get a platinum doublet as opposed to going straight to the docetaxel/ramucirumab.

Mark A. Socinski, MD: I completely agree.

Thomas E. Stinchcombe, MD: I completely agree.

Mark A. Socinski, MD: That’s an excellent point. Suresh?

Suresh Senan, MRCP, FRCR, PhD: There’s emerging data from the Yale Group regarding patients who have slow progression. It’s a small publication. A series of 26 patients in the Journal of Thoracic Oncology [JTO] administered local therapy on slow progression. Many of them could continue, even with long disease remission. Control rates were either with or without the same I-O. It’s emerging data, but I’d be interested to see what the others think about patients who are slow progressing. Do you just abandon chemotherapy and I-O/I-O combinations? Or is there a group where you should consider local therapy, and then proceed just like we do with patients who have driver mutations?

Mark A. Socinski, MD: It follows the same paradigm. That’s something I certainly consider in patients if they have either slow progression or a solitary site, or maybe 2 sites, in which the downside of doing targeted radiotherapy is very small. It doesn’t add much in the way of toxicity. We’ve certainly done that and continued beyond it. I’m aware of the Yale Experience. What do others think of that? It’s something that we started in the patients with EGFR [epithelial growth factor receptor]- and ALK [anaplastic lymphoma kinas]-mutations, where we had a single site either in the brain or elsewhere. You would radiate it and continue systemic therapy, thinking that most of the disease was controlled; however, these sites may, for whatever reason, be resistant to the treatment.

Maximilian Hochmair, MD: I’m completely in line with you that we learned from patients who have EGFR-, ALK- or ROS1 [c-ros oncogene tyrosine kinase receptor]-mutations that this strategy with PFS1 and 2 works. When we do a local treatment in a local progression, this clone appears. We treat that clone, ideally, with the same regimen. We are doing that for patients on I-O, but it’s only a small piece of the patients that show this progression type.

Leora Horn, MD, MSc, FRCPC: You need to make sure they are progressing because we’ve had instances where it looks like a patient is progressing even at 12 and 18 months, and we diagnosed granulomatous disease. We’ve diagnosed a new metastatic from a different tumor type. Before you do that local therapy, it’s important to biopsy, to make sure you’re doing the right thing for the patient.

Mark A. Socinski, MD: Which we don’t always do, right?

Leora Horn, MD, MSc, FRCPC: Right.

Transcript Edited for Clarity 

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Transcript: 

Maximilian Hochmair, MD: We were talking about pseudoprogression in the beginning of treatment. It does not occur as often as we thought; it’s about 3% to 5% of our patients when we collected data. The decision is always important if there’s a progression; we should switch to chemotherapy. When we do the combination then, it’s not that clinically relevant. From my point of view, the pseudoprogression will happen in the beginning, but in the longer period I did not see pseudoprogression. After half a year and we see progression, it’s real progression and not pseudoprogression.

Mark A. Socinski, MD: I agree. We are oversold on pseudoprogression in lung cancer. The issue that I wanted to get your opinion on is hyperprogression, which is real. Around 5% of the patient population may have hyperprogression. We struggle with what the true definition is, but we know it’s real in clinical practice. What are your thoughts?

Maximilian Hochmair, MD: We had a poster at the European Society of Medical Oncology [ESMO] 2018 annual meeting about this fact that we can measure it with biomarkers—CTL4 [cytotoxic T-lymphocyte-associated protein 4] cells. It’s a clinical and relevant issue because we have to be able to identify pseudo- from hyperprogression. In my clinic, those patients sometimes run away fast and you cannot stop them.

Mark A. Socinski, MD: We don’t understand the mechanisms of resistance to immunotherapy [I-O] agents. It’s different if you have a patient who’s maybe been on I-O for 18 months and then progresses. That’s different obviously from the other end of the spectrum where you progress in the first 6 weeks. I don’t know that we understand the biologic differences from those sorts of things. There is some data, getting back to docetaxel [Taxotere] and ramucirumab [Cyramza], from an unplanned retrospective analysis on how rapidly you progress after first-line treatment. There was some evidence that if you transition to second-line therapy treatment, there was activity with docetaxel/ramucirumab in that population. Thoughts about this?

Maximilian Hochmair, MD: In the nintedanib [OFEV] data in the LUME-Lung 1 trial we saw the same thing. When the patients progressed in the first 6 months, the antiangiogenic drug worked much better. For those patients who are fast progressing, they need ramucirumab or nintedanib.

Mark A. Socinski, MD: That’s the take-home message: for patients who progress quickly, there’s still an option from which they may benefit. It probably is the combination of docetaxel with an antiangiogenic agent in that setting.

Leora Horn, MD, MSc, FRCPC: Although, the one thing to consider is the patients with hyperprogression benefit more from a single agent than combination therapies.

Mark A. Socinski, MD: Yes.

Leora Horn, MD, MSc, FRCPC: If they progress on a single agent, they should get a platinum doublet as opposed to going straight to the docetaxel/ramucirumab.

Mark A. Socinski, MD: I completely agree.

Thomas E. Stinchcombe, MD: I completely agree.

Mark A. Socinski, MD: That’s an excellent point. Suresh?

Suresh Senan, MRCP, FRCR, PhD: There’s emerging data from the Yale Group regarding patients who have slow progression. It’s a small publication. A series of 26 patients in the Journal of Thoracic Oncology [JTO] administered local therapy on slow progression. Many of them could continue, even with long disease remission. Control rates were either with or without the same I-O. It’s emerging data, but I’d be interested to see what the others think about patients who are slow progressing. Do you just abandon chemotherapy and I-O/I-O combinations? Or is there a group where you should consider local therapy, and then proceed just like we do with patients who have driver mutations?

Mark A. Socinski, MD: It follows the same paradigm. That’s something I certainly consider in patients if they have either slow progression or a solitary site, or maybe 2 sites, in which the downside of doing targeted radiotherapy is very small. It doesn’t add much in the way of toxicity. We’ve certainly done that and continued beyond it. I’m aware of the Yale Experience. What do others think of that? It’s something that we started in the patients with EGFR [epithelial growth factor receptor]- and ALK [anaplastic lymphoma kinas]-mutations, where we had a single site either in the brain or elsewhere. You would radiate it and continue systemic therapy, thinking that most of the disease was controlled; however, these sites may, for whatever reason, be resistant to the treatment.

Maximilian Hochmair, MD: I’m completely in line with you that we learned from patients who have EGFR-, ALK- or ROS1 [c-ros oncogene tyrosine kinase receptor]-mutations that this strategy with PFS1 and 2 works. When we do a local treatment in a local progression, this clone appears. We treat that clone, ideally, with the same regimen. We are doing that for patients on I-O, but it’s only a small piece of the patients that show this progression type.

Leora Horn, MD, MSc, FRCPC: You need to make sure they are progressing because we’ve had instances where it looks like a patient is progressing even at 12 and 18 months, and we diagnosed granulomatous disease. We’ve diagnosed a new metastatic from a different tumor type. Before you do that local therapy, it’s important to biopsy, to make sure you’re doing the right thing for the patient.

Mark A. Socinski, MD: Which we don’t always do, right?

Leora Horn, MD, MSc, FRCPC: Right.

Transcript Edited for Clarity 
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