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Looking at the IMpower Data in NSCLC

Panelists: Mark A. Socinski, MD, Advent Health Cancer Institute; John V. Heymach, MD, PhD, MD Anderson Cancer Center; Leora Horn, MD, MSc, FRCPC, Vanderbilt University Medical Center; Mohammad Jahanzeb, MD, University of Miami Health System; Heather A. Wakelee, MD, Stanford University Medical Center; Jarushka Naidoo, MBBCh, Sidney Kimmel Cancer Center
Published: Wednesday, Mar 27, 2019



Transcript: 

Mark A. Socinski, MD: I wanted to get John’s perspective on the IMpower150. The reason 150 was done was because of the observations about a high VEGF, and how it could be relatively immunosuppressive as a term; but the concept of using anti-VEGF therapy with immunotherapy, obviously that was what 150 tested. Your thoughts?

John V. Heymach, MD, PhD: I think it’s a great point, and the first thing to mention about IMpower150, if you look at the relative benefit compared to the control arm, it isn’t as great as KEYNOTE-189, but the control arm is different. The control arm contains bevacizumab in IMpower150. Now we know bevacizumab adds substantial benefit in this setting. There’s a lot of data saying that VEGF in addition to helping blood vessels grow is immunosuppressive and it works through myeloid cells and other populations. So the combination should in theory enhance immune response.

And the data are consistent with that possibility. I think where it’s most intriguing is the EGFR mutants. There’s a lot of data that EGFR mutants may be particularly sensitive to VEGF inhibition. If you go back and look at the beta trial, the group that benefited the most from bevacizumab and erlotinib were the EGFR mutants. And we now have several randomized phase II studies that at least show a PFS [progression-free survival] benefit for adding VEGF inhibition with EGFR. So we think EGFR mutants are really more VEGF driven than other tumor types.

And so it was encouraging that in IMpower150, the addition of immunotherapy really did seem to add benefit for the EGFR mutants, but that may be because VEGF inhibition is onboard.

Mark A. Socinski, MD: Exactly.

John V. Heymach, MD, PhD: So that combination of VEGF and PD-L1 [programmed death-ligand 1] blockade, may be particularly effective for EGFR mutants. Now I think there’s a number of EGFR-focused trials now with immunotherapy combinations going on. And so we’re excited to really ask that in a properly powered way devoted to EGFR mutants. But that’s why I think for EGFR mutants in particular, that’s one right now that has the best data supporting it. Now the FDA label is a different issue, and why it was removed from label. But at least if you said what data do we have for EGFR mutants with immunotherapy and chemotherapy, that’s really the best data.

Mark A. Socinski, MD: That’s really IMpower150. When you get to the point where you’ve exhausted your TKI [tyrosine kinase inhibitor], a possibility is that this is an option for those patients eligible for bevacizumab, that’s the key point.

Jarushka Naidoo, MBBCh: I think the other point that supports that is the other study that did enroll EGFR and ALK treated patients, IMpower130, which was a platinum, taxane, and atezolizumab. And there was no PFS or OS [overall survival] benefit there. So perhaps it is the VEGF that’s making the difference.

Mark A. Socinski, MD: And we haven’t talked about arm A of 150, but that was the same observation on that trial.

Transcript Edited for Clarity

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Transcript: 

Mark A. Socinski, MD: I wanted to get John’s perspective on the IMpower150. The reason 150 was done was because of the observations about a high VEGF, and how it could be relatively immunosuppressive as a term; but the concept of using anti-VEGF therapy with immunotherapy, obviously that was what 150 tested. Your thoughts?

John V. Heymach, MD, PhD: I think it’s a great point, and the first thing to mention about IMpower150, if you look at the relative benefit compared to the control arm, it isn’t as great as KEYNOTE-189, but the control arm is different. The control arm contains bevacizumab in IMpower150. Now we know bevacizumab adds substantial benefit in this setting. There’s a lot of data saying that VEGF in addition to helping blood vessels grow is immunosuppressive and it works through myeloid cells and other populations. So the combination should in theory enhance immune response.

And the data are consistent with that possibility. I think where it’s most intriguing is the EGFR mutants. There’s a lot of data that EGFR mutants may be particularly sensitive to VEGF inhibition. If you go back and look at the beta trial, the group that benefited the most from bevacizumab and erlotinib were the EGFR mutants. And we now have several randomized phase II studies that at least show a PFS [progression-free survival] benefit for adding VEGF inhibition with EGFR. So we think EGFR mutants are really more VEGF driven than other tumor types.

And so it was encouraging that in IMpower150, the addition of immunotherapy really did seem to add benefit for the EGFR mutants, but that may be because VEGF inhibition is onboard.

Mark A. Socinski, MD: Exactly.

John V. Heymach, MD, PhD: So that combination of VEGF and PD-L1 [programmed death-ligand 1] blockade, may be particularly effective for EGFR mutants. Now I think there’s a number of EGFR-focused trials now with immunotherapy combinations going on. And so we’re excited to really ask that in a properly powered way devoted to EGFR mutants. But that’s why I think for EGFR mutants in particular, that’s one right now that has the best data supporting it. Now the FDA label is a different issue, and why it was removed from label. But at least if you said what data do we have for EGFR mutants with immunotherapy and chemotherapy, that’s really the best data.

Mark A. Socinski, MD: That’s really IMpower150. When you get to the point where you’ve exhausted your TKI [tyrosine kinase inhibitor], a possibility is that this is an option for those patients eligible for bevacizumab, that’s the key point.

Jarushka Naidoo, MBBCh: I think the other point that supports that is the other study that did enroll EGFR and ALK treated patients, IMpower130, which was a platinum, taxane, and atezolizumab. And there was no PFS or OS [overall survival] benefit there. So perhaps it is the VEGF that’s making the difference.

Mark A. Socinski, MD: And we haven’t talked about arm A of 150, but that was the same observation on that trial.

Transcript Edited for Clarity
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