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Maintenance Therapy for Advanced Nonsquamous NSCLC

Panelists: Mark A. Socinski, MD, AdventHealth Cancer Institute; Paul K. Paik, MD, Memorial Sloan Kettering Cancer Center; Kristin Higgins, MD, Emory Healthcare; Corey J. Langer, MD, Hospital of the University of Pennsylvania; Heather A. Wakelee, MD, Stanford University Medical Center; Ticiana A. Leal, MD, University of Wisconsin School of Medicine and Public Health
Published: Wednesday, Jul 24, 2019



Transcript: 

Mark A. Socinski, MD: We’ll all admit that our practices do have patients who are not eligible for immunotherapy. We do have….

Paul K. Paik, MD: Overall.

Mark A. Socinski, MD: So Ticiana, talk about ECOG 5508. This was really interesting 10 years ago. We are finally going to see data. It’s still pertinent to practice, right? We would all agree with that. Tell us about it.

Ticiana A. Leal, MD: ECOG 5508 is a positive group trial, and it’s a study that really sought out, at the time, to identify the optimal maintenance therapy for patients with advanced, nonsquamous non–small cell lung cancer. This was a phase III trial that randomized patients after completion of induction with carboplatin/paclitaxel/bevacizumab to bevacizumab or pemetrexed or the combination of bevacizumab and pemetrexed. Initially, in the abstract format, we’re seeing that the combination of pemetrexed and bevacizumab did not show an overall survival benefit. And we’ll hear more at the session on Monday. Dr Ramalingam from Emory University will be presenting that data, so we’re excited to hear about it. I think it still is relevant. I think it was something that, in real life, we have really thought about. There are patients that don’t get immunotherapy because there are contraindications. I would say it still is about 15% to 20% of the population. I think we’re going to hear more about patients with autoimmune diseases, but that’s a population for which we have in our clinic that we still don’t know the real answer of: Are they eligible?

Mark A. Socinski, MD: Right.

Corey J. Langer, MD: A substantial proportion of our patients, for one reason or another, cannot get immunotherapy, and I think these data are still applicable. They’re still relevant. And they are incredibly mature. We’re talking about a median of 4 to 5 years follow up. So we actually are going to see 5-year data as part of this trial. And I think because the details of the study are embargoed, and we know in the abstract that it does not include that, I think we have the potential of being fairly impressed. There’s 1 other trial from Japan that was essentially a similar design, but it used a different foundation regimen. It was not paclitaxel/carboplatin/bevacizumab, but pemetrexed/carboplatin/bevacizumab. It was a randomization of bevacizumab plus pemetrexed versus the control.

We saw the incorporation of pemetrexed plus bevacizumab in those who had established EGFR wild-type disease. So again, a potential group that we know about, but didn’t know about in the era of ECOG 5508. We weren’t routinely testing for EGFR. Certainly in East Asia it’s part of the standard. In a subpopulation there, they did in fact see a survival benefit. So there are nuances here that I think we still need to explore. As a general principle, it appears that single-agent—either bevacizumab or pemetrexed—is probably de facto equivalence in the maintenance setting. We should give some sort of maintenance if we can. We probably can no longer argue for using the combination routinely, although maybe in selected patients. One might make that argument. And I think that needs to be explored further.

Heather A. Wakelee, MD: I might disagree with you a little bit. I think the era of the switch maintenance is behind us, right? But I think that for patients who have been on carboplatin/pemetrexed/bevacizumab, which was the Japanese study using that backbone, and then the continuation maintenance question of bevacizumab or pemetrexed/bevacizumab, for patients who aren’t getting immune therapy, that’s still a very relevant question.

Corey J. Langer, MD: Oh, I agree.

Heather A. Wakelee, MD: They did pull out only the EGFR wild-type, but they had a very small number of patients with EGFR mutations who went on the study. It was less than 10%. So just sort of taking that section out, the majority of the patients on the study, looking at that subset, did have a significant benefit with the 2 drugs and not just bevacizumab.

Corey J. Langer, MD: The historic trial, AVAPERL, really asked the same question….

Heather A. Wakelee, MD: Yes, exactly.

Corey J. Langer, MD: Significant PFS [progression-free survival] benefit. There was no OS [overall survival] benefit overall, but it was underpowered for survival. It really wasn’t primarily powered.

Mark A. Socinski, MD: Maybe a trend.

Corey J. Langer, MD: Clearly a trend. So this is still something of an open question. I personally have patients in my clinic who are getting to know each other. They are long-term survivors on some sort of maintenance therapy. It usually started out as a combination for one reason or another, either logistics or some cumulative toxicity. Many are just on 1 agent, but my record is 10 years and counting.

Heather A. Wakelee, MD: I’ve got some long-term patients too. It’s going to be interesting because, in my practice, the patients who are most often getting carboplatin/pemetrexed/bevacizumab are my EGFR mutation disease patients who have already been through their EGFR inhibitors. Sometimes you talk about IMpower150, but you don’t want to lose hair. We know about the VEGF inhibition here. So that’s still often a very common regimen. It’s interesting that maybe that group doesn’t need the pemetrexed maintenance. But subsets of subsets....

Corey J. Langer, MD: Certainly, before IMpower150, my go-to regimen in TKI [tyrosine kinase inhibitor]-refractory patients was bevacizumab in combination, generally, with pemetrexed/carboplatin.

Heather A. Wakelee, MD: Yes.

Transcript Edited for Clarity

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Transcript: 

Mark A. Socinski, MD: We’ll all admit that our practices do have patients who are not eligible for immunotherapy. We do have….

Paul K. Paik, MD: Overall.

Mark A. Socinski, MD: So Ticiana, talk about ECOG 5508. This was really interesting 10 years ago. We are finally going to see data. It’s still pertinent to practice, right? We would all agree with that. Tell us about it.

Ticiana A. Leal, MD: ECOG 5508 is a positive group trial, and it’s a study that really sought out, at the time, to identify the optimal maintenance therapy for patients with advanced, nonsquamous non–small cell lung cancer. This was a phase III trial that randomized patients after completion of induction with carboplatin/paclitaxel/bevacizumab to bevacizumab or pemetrexed or the combination of bevacizumab and pemetrexed. Initially, in the abstract format, we’re seeing that the combination of pemetrexed and bevacizumab did not show an overall survival benefit. And we’ll hear more at the session on Monday. Dr Ramalingam from Emory University will be presenting that data, so we’re excited to hear about it. I think it still is relevant. I think it was something that, in real life, we have really thought about. There are patients that don’t get immunotherapy because there are contraindications. I would say it still is about 15% to 20% of the population. I think we’re going to hear more about patients with autoimmune diseases, but that’s a population for which we have in our clinic that we still don’t know the real answer of: Are they eligible?

Mark A. Socinski, MD: Right.

Corey J. Langer, MD: A substantial proportion of our patients, for one reason or another, cannot get immunotherapy, and I think these data are still applicable. They’re still relevant. And they are incredibly mature. We’re talking about a median of 4 to 5 years follow up. So we actually are going to see 5-year data as part of this trial. And I think because the details of the study are embargoed, and we know in the abstract that it does not include that, I think we have the potential of being fairly impressed. There’s 1 other trial from Japan that was essentially a similar design, but it used a different foundation regimen. It was not paclitaxel/carboplatin/bevacizumab, but pemetrexed/carboplatin/bevacizumab. It was a randomization of bevacizumab plus pemetrexed versus the control.

We saw the incorporation of pemetrexed plus bevacizumab in those who had established EGFR wild-type disease. So again, a potential group that we know about, but didn’t know about in the era of ECOG 5508. We weren’t routinely testing for EGFR. Certainly in East Asia it’s part of the standard. In a subpopulation there, they did in fact see a survival benefit. So there are nuances here that I think we still need to explore. As a general principle, it appears that single-agent—either bevacizumab or pemetrexed—is probably de facto equivalence in the maintenance setting. We should give some sort of maintenance if we can. We probably can no longer argue for using the combination routinely, although maybe in selected patients. One might make that argument. And I think that needs to be explored further.

Heather A. Wakelee, MD: I might disagree with you a little bit. I think the era of the switch maintenance is behind us, right? But I think that for patients who have been on carboplatin/pemetrexed/bevacizumab, which was the Japanese study using that backbone, and then the continuation maintenance question of bevacizumab or pemetrexed/bevacizumab, for patients who aren’t getting immune therapy, that’s still a very relevant question.

Corey J. Langer, MD: Oh, I agree.

Heather A. Wakelee, MD: They did pull out only the EGFR wild-type, but they had a very small number of patients with EGFR mutations who went on the study. It was less than 10%. So just sort of taking that section out, the majority of the patients on the study, looking at that subset, did have a significant benefit with the 2 drugs and not just bevacizumab.

Corey J. Langer, MD: The historic trial, AVAPERL, really asked the same question….

Heather A. Wakelee, MD: Yes, exactly.

Corey J. Langer, MD: Significant PFS [progression-free survival] benefit. There was no OS [overall survival] benefit overall, but it was underpowered for survival. It really wasn’t primarily powered.

Mark A. Socinski, MD: Maybe a trend.

Corey J. Langer, MD: Clearly a trend. So this is still something of an open question. I personally have patients in my clinic who are getting to know each other. They are long-term survivors on some sort of maintenance therapy. It usually started out as a combination for one reason or another, either logistics or some cumulative toxicity. Many are just on 1 agent, but my record is 10 years and counting.

Heather A. Wakelee, MD: I’ve got some long-term patients too. It’s going to be interesting because, in my practice, the patients who are most often getting carboplatin/pemetrexed/bevacizumab are my EGFR mutation disease patients who have already been through their EGFR inhibitors. Sometimes you talk about IMpower150, but you don’t want to lose hair. We know about the VEGF inhibition here. So that’s still often a very common regimen. It’s interesting that maybe that group doesn’t need the pemetrexed maintenance. But subsets of subsets....

Corey J. Langer, MD: Certainly, before IMpower150, my go-to regimen in TKI [tyrosine kinase inhibitor]-refractory patients was bevacizumab in combination, generally, with pemetrexed/carboplatin.

Heather A. Wakelee, MD: Yes.

Transcript Edited for Clarity
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