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Surgery Options for NSCLC & I-O Therapy in EGFR-Mutations

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: Monday, Dec 10, 2018



Transcript: 

Mark A. Socinski, MD: I don’t want to get into the role of surgery in stage III disease, particularly the stage IIIA disease, because my personal bias is that there’s a limited role for surgery in that setting; it’s a chemoradiotherapy disease; surgeons will argue that. Does this data influence who you might consider for surgery? Or is it a different argument?

Maximilian Hochmair, MD: We do not have good data for chemoradiation I-O. We should try to avoid surgery a bit more. Sometimes the surgeon on the tumor board would say, “I want to do surgery.” But this data help us side on the nonsurgeon’s part.

Thomas E. Stinchcombe, MD: We have a disciplined group of people who considered surgery for single-stations microscopic N2 disease, fraught with induction therapy. Many of them received postoperative radiation therapy, or at least a referral to a radiation oncologist. It doesn’t change our strategy at this point.

Mark A. Socinski, MD: Because you were limiting surgeries to the low-volume single-station?

Thomas E. Stinchcombe, MD: Yes.

Leora Horn, MD, MSc, FRCPC: We were the same. We would do local induction chemoradiation, but it’s rare. The majority of patients are not being considered for surgery; they’re being administered chemoradiation and durvalumab [Imfinzi].

Mark A. Socinski, MD: From a radiation oncology point of view?

Suresh Senan, MRCP, FRCR, PhD: From the National System for Veterans’ Care in the Netherlands, we’ve decreased surgery tremendously, but this would be an extra reason not to do it. We do it for selective patients for whom you can achieve a lobectomy single station—but then there’s the question based on some of the animal work, suggesting that actually, in animal models, if you do a surgical procedure, the micrometastases actually stimulate it. It would be interesting to see the adjuvant survival trials and how the control arms are going to perform versus the I-O arms and whether there will be much of a difference.

Mark A. Socinski, MD: Then the other opinion is the PACIFIC trial, in which 6% of the patients had EGFR-mutation-positive disease that was included in the trial; it’s a small subset. It was one of the widest confidence intervals on the Forest Plot in terms of patients with EGFR-mutation. What do you do in your practice? If you had a patient with EGFR mutation, maybe we shouldn’t be testing in stage III disease. Would you apply the PACIFIC data to these patient populations?

Leora Horn, MD, MSc, FRCPC: They’re a harder group of patients to deal with. The progression-free survival data weren’t positive. The overall survival data we do not have because the numbers were so small. I worry that these I-O agents are not effective in first line. We’ve seen with the data from Eddie Garin, MD, that they’re not that effective second or third line in some Keynote Checkmate studies. It’s a discussion we need to have with those patients because the other thing you worry about is progression and administering tyrosine kinase inhibitors [TKIs].

Mark A. Socinski, MD: Hopefully they don’t.

Leora Horn, MD, MSc, FRCPC: Unfortunately, the hazard ratio was good but not perfect.

Mark A. Socinski, MD: That’s the point.

Leora Horn, MD, MSc, FRCPC: OK, you give that TKI and then they have enhanced toxicity from the TKI.

Mark A. Socinski, MD: The question is, does the chemotherapy alter the immune milieu and create a different situation from what we’ve typically seen with the data on monotherapy in second line for patients with EGFR mutations. I don’t know the answer to that.

Leora Horn, MD, MSc, FRCPC: I don’t think you’re harming the patient by doing it.

Maximilian Hochmair, MD: From my point of view, we are testing in other stages also, so when we do a bronchoscopy, we consult the whole panel. We don’t just test in stage IV. We get the EGFR-mutation testing immediately in all of our patients. We also have data from a phase II trial using afatinib [Gilotrif] as an induction treatment 3 months before the chemoradiotherapy or in combination with surgery. In this situation, we think about doing an induction with EGFR TKIs. These patients with EGFR mutations do not do as well with I-O; I would avoid it in this situation generally.

Mark A. Socinski, MD: We don’t have enough data to say one way or the other.

Suresh Senan, MRCP, FRCR, PhD: We’ve had this debate many times: If it’s not true stage III, we’ll go to concurrent chemoradiotherapy, etoposide [Etopophos].

It becomes difficult with the I-O now, to know whether we should add it. I’m in favor of it because it has not yielded adverse side effects. Our experience has been, when we do chemoradiotherapy in patients with EGFR mutation, rather bad results with fairly soon recurrence.

Occasionally we have patients with bulky disease; they sometimes begin with an EGFR inhibitor followed by an induction phase, which we do concurrently since it’s localized disease. We shouldn’t be treating it the same as stage IV disease.

Transcript Edited for Clarity 

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Transcript: 

Mark A. Socinski, MD: I don’t want to get into the role of surgery in stage III disease, particularly the stage IIIA disease, because my personal bias is that there’s a limited role for surgery in that setting; it’s a chemoradiotherapy disease; surgeons will argue that. Does this data influence who you might consider for surgery? Or is it a different argument?

Maximilian Hochmair, MD: We do not have good data for chemoradiation I-O. We should try to avoid surgery a bit more. Sometimes the surgeon on the tumor board would say, “I want to do surgery.” But this data help us side on the nonsurgeon’s part.

Thomas E. Stinchcombe, MD: We have a disciplined group of people who considered surgery for single-stations microscopic N2 disease, fraught with induction therapy. Many of them received postoperative radiation therapy, or at least a referral to a radiation oncologist. It doesn’t change our strategy at this point.

Mark A. Socinski, MD: Because you were limiting surgeries to the low-volume single-station?

Thomas E. Stinchcombe, MD: Yes.

Leora Horn, MD, MSc, FRCPC: We were the same. We would do local induction chemoradiation, but it’s rare. The majority of patients are not being considered for surgery; they’re being administered chemoradiation and durvalumab [Imfinzi].

Mark A. Socinski, MD: From a radiation oncology point of view?

Suresh Senan, MRCP, FRCR, PhD: From the National System for Veterans’ Care in the Netherlands, we’ve decreased surgery tremendously, but this would be an extra reason not to do it. We do it for selective patients for whom you can achieve a lobectomy single station—but then there’s the question based on some of the animal work, suggesting that actually, in animal models, if you do a surgical procedure, the micrometastases actually stimulate it. It would be interesting to see the adjuvant survival trials and how the control arms are going to perform versus the I-O arms and whether there will be much of a difference.

Mark A. Socinski, MD: Then the other opinion is the PACIFIC trial, in which 6% of the patients had EGFR-mutation-positive disease that was included in the trial; it’s a small subset. It was one of the widest confidence intervals on the Forest Plot in terms of patients with EGFR-mutation. What do you do in your practice? If you had a patient with EGFR mutation, maybe we shouldn’t be testing in stage III disease. Would you apply the PACIFIC data to these patient populations?

Leora Horn, MD, MSc, FRCPC: They’re a harder group of patients to deal with. The progression-free survival data weren’t positive. The overall survival data we do not have because the numbers were so small. I worry that these I-O agents are not effective in first line. We’ve seen with the data from Eddie Garin, MD, that they’re not that effective second or third line in some Keynote Checkmate studies. It’s a discussion we need to have with those patients because the other thing you worry about is progression and administering tyrosine kinase inhibitors [TKIs].

Mark A. Socinski, MD: Hopefully they don’t.

Leora Horn, MD, MSc, FRCPC: Unfortunately, the hazard ratio was good but not perfect.

Mark A. Socinski, MD: That’s the point.

Leora Horn, MD, MSc, FRCPC: OK, you give that TKI and then they have enhanced toxicity from the TKI.

Mark A. Socinski, MD: The question is, does the chemotherapy alter the immune milieu and create a different situation from what we’ve typically seen with the data on monotherapy in second line for patients with EGFR mutations. I don’t know the answer to that.

Leora Horn, MD, MSc, FRCPC: I don’t think you’re harming the patient by doing it.

Maximilian Hochmair, MD: From my point of view, we are testing in other stages also, so when we do a bronchoscopy, we consult the whole panel. We don’t just test in stage IV. We get the EGFR-mutation testing immediately in all of our patients. We also have data from a phase II trial using afatinib [Gilotrif] as an induction treatment 3 months before the chemoradiotherapy or in combination with surgery. In this situation, we think about doing an induction with EGFR TKIs. These patients with EGFR mutations do not do as well with I-O; I would avoid it in this situation generally.

Mark A. Socinski, MD: We don’t have enough data to say one way or the other.

Suresh Senan, MRCP, FRCR, PhD: We’ve had this debate many times: If it’s not true stage III, we’ll go to concurrent chemoradiotherapy, etoposide [Etopophos].

It becomes difficult with the I-O now, to know whether we should add it. I’m in favor of it because it has not yielded adverse side effects. Our experience has been, when we do chemoradiotherapy in patients with EGFR mutation, rather bad results with fairly soon recurrence.

Occasionally we have patients with bulky disease; they sometimes begin with an EGFR inhibitor followed by an induction phase, which we do concurrently since it’s localized disease. We shouldn’t be treating it the same as stage IV disease.

Transcript Edited for Clarity 
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