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ADRIATIC Trial in Locally Advanced Small-Cell Lung Cancer

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: Tuesday, Apr 09, 2019



Transcript: 

Mark A. Socinski, MD: So what are people’s thoughts in the wake of the PACIFIC trial? Should we do a PACIFIC small-cell lung cancer trial?

Leora Horn, MD, MSc, FRCPC: They’re doing it. It’s called ADRIATIC.

Mark A. Socinski, MD: I know.

Leora Horn, MD, MSc, FRCPC: I think it may not accrue as quickly as PACIFIC did.

Mark A. Socinski, MD: Well, I was going to say, do we know the status of the sea change?

Leora Horn, MD, MSc, FRCPC: It’s open to accrual. We’re opening it at our institution at the moment. Those patients are definitely not as common.

Mark A. Socinski, MD: And remind me of the design, the exact design. Is it very much like PACIFIC?

Leora Horn, MD, MSc, FRCPC:  It is identical to PACIFIC. So concurrent chemoradiation therapy and after our patients are going on durvalumab.

Heather A. Wakelee, MD: But are they getting 4 cycles of chemotherapy? Because I think that’s one of the challenges is that for locally advanced non­–small cell lung cancer, we’re comfortable with this idea that if you give 2 cycles of cisplatin etoposide, that’s adequate because we’ve not been able to show that giving additional chemo is beneficial. But in small cell we always give 4 cycles.

Mark A. Socinski, MD: But I would, I don’t know what the trial design is, but I would be comfortable in a small-cell patient giving the radiotherapy, starting cycle 3.

Heather A. Wakelee, MD: Yes.

Mark A. Socinski, MD: And doing that and then starting the immunotherapy. I don’t know if that’s the design or what.

Mohammad Jahanzeb, MD: I think Marie had done a randomized trial, from Canada, British Columbia. Second versus fifth cycle. And that showed superiority of second, but second versus third may not be that different.

Mark A. Socinski, MD: Well we did, back when I was at Carolina, one of the radiation oncology residents did a meta-analysis. You know that old saying: you never met an analysis you didn’t like. This was a small cell where we looked at early versus late. And early was defined as any time starting radiotherapy in the first 3 cycles. And there clearly was a benefit. It was not necessarily magic to give it cycle 1, but early on in the course. So I think the data would support a cycle 3.

John V. Heymach, MD, PhD: Yeah. And you know we’ve recently completed a small-cell limited stage trial of chemo with radiation and pembrolizumab at the same time. And in small cell it’s the toxicity is even more of a concern. First of all, patients tend to have more comorbidities, worse pulmonary function. But the radiation fields tend to be larger for small cell as well because you really have to radiate more of the mediastinum.

And Jim Welsh, MD, has presented some of this data publicly. But it was good to see that it was also tolerated. We did have a case of pericarditis where we learned to be a little bit more careful with the heart dose. But the good is you can give chemo, radiation, and immunotherapy together, and it’s tolerable, and there will be randomized studies that come out in the near future that tell us whether it adds benefit. But at least we know it can be done.

Heather A. Wakelee, MD: I think we still have to be a little bit cautious though. I mean going back to non–small cell where there’s also lots of studies now ongoing looking at concurrent chemotherapy radiation and immune therapy, while the early results are promising, there’s definitely the toxicity is higher. And so I think we need to be cautious not to say that it’s safe and we can do it, until we get a little bit more. Maybe I’m just being a bit more old school than you, but I just, I think we need to be cautious still. These are not things that should necessarily be done widely in the community yet.

John V. Heymach, MD, PhD: Well yeah, I mean, just to be clear, obviously we need to get the randomized data to say if it prolongs overall survival. But when you’re dealing with a patient population where the vast majority end up recurring, you know our long-term cure rates for small cell are in the neighborhood of 10% to 20% depending on the studies. And for non–small cell with chemoradiation, a touch higher than that. I think it merits an aggressive approach if we’re really trying to increase cure rates, and that’s the goal here. So I certainly wouldn’t say to dismiss the toxicities, but if we do have a chance to increase cures, I think we need to be mindful, but not slow going into these things.

Heather A. Wakelee, MD: No, but the trials are accruing and I just think we need to be cautious. I mean in small cell I think there were a lot of people who assumed that the maintenance was going to be a positive trial and it wasn’t, right? So we can’t always assume that it’s going to be better.

Mark A. Socinski, MD: We shouldn’t be swayed by the old saying, you know, “Don’t confuse me with the data, I know what I’m doing.”

Transcript Edited for Clarity

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Transcript: 

Mark A. Socinski, MD: So what are people’s thoughts in the wake of the PACIFIC trial? Should we do a PACIFIC small-cell lung cancer trial?

Leora Horn, MD, MSc, FRCPC: They’re doing it. It’s called ADRIATIC.

Mark A. Socinski, MD: I know.

Leora Horn, MD, MSc, FRCPC: I think it may not accrue as quickly as PACIFIC did.

Mark A. Socinski, MD: Well, I was going to say, do we know the status of the sea change?

Leora Horn, MD, MSc, FRCPC: It’s open to accrual. We’re opening it at our institution at the moment. Those patients are definitely not as common.

Mark A. Socinski, MD: And remind me of the design, the exact design. Is it very much like PACIFIC?

Leora Horn, MD, MSc, FRCPC:  It is identical to PACIFIC. So concurrent chemoradiation therapy and after our patients are going on durvalumab.

Heather A. Wakelee, MD: But are they getting 4 cycles of chemotherapy? Because I think that’s one of the challenges is that for locally advanced non­–small cell lung cancer, we’re comfortable with this idea that if you give 2 cycles of cisplatin etoposide, that’s adequate because we’ve not been able to show that giving additional chemo is beneficial. But in small cell we always give 4 cycles.

Mark A. Socinski, MD: But I would, I don’t know what the trial design is, but I would be comfortable in a small-cell patient giving the radiotherapy, starting cycle 3.

Heather A. Wakelee, MD: Yes.

Mark A. Socinski, MD: And doing that and then starting the immunotherapy. I don’t know if that’s the design or what.

Mohammad Jahanzeb, MD: I think Marie had done a randomized trial, from Canada, British Columbia. Second versus fifth cycle. And that showed superiority of second, but second versus third may not be that different.

Mark A. Socinski, MD: Well we did, back when I was at Carolina, one of the radiation oncology residents did a meta-analysis. You know that old saying: you never met an analysis you didn’t like. This was a small cell where we looked at early versus late. And early was defined as any time starting radiotherapy in the first 3 cycles. And there clearly was a benefit. It was not necessarily magic to give it cycle 1, but early on in the course. So I think the data would support a cycle 3.

John V. Heymach, MD, PhD: Yeah. And you know we’ve recently completed a small-cell limited stage trial of chemo with radiation and pembrolizumab at the same time. And in small cell it’s the toxicity is even more of a concern. First of all, patients tend to have more comorbidities, worse pulmonary function. But the radiation fields tend to be larger for small cell as well because you really have to radiate more of the mediastinum.

And Jim Welsh, MD, has presented some of this data publicly. But it was good to see that it was also tolerated. We did have a case of pericarditis where we learned to be a little bit more careful with the heart dose. But the good is you can give chemo, radiation, and immunotherapy together, and it’s tolerable, and there will be randomized studies that come out in the near future that tell us whether it adds benefit. But at least we know it can be done.

Heather A. Wakelee, MD: I think we still have to be a little bit cautious though. I mean going back to non–small cell where there’s also lots of studies now ongoing looking at concurrent chemotherapy radiation and immune therapy, while the early results are promising, there’s definitely the toxicity is higher. And so I think we need to be cautious not to say that it’s safe and we can do it, until we get a little bit more. Maybe I’m just being a bit more old school than you, but I just, I think we need to be cautious still. These are not things that should necessarily be done widely in the community yet.

John V. Heymach, MD, PhD: Well yeah, I mean, just to be clear, obviously we need to get the randomized data to say if it prolongs overall survival. But when you’re dealing with a patient population where the vast majority end up recurring, you know our long-term cure rates for small cell are in the neighborhood of 10% to 20% depending on the studies. And for non–small cell with chemoradiation, a touch higher than that. I think it merits an aggressive approach if we’re really trying to increase cure rates, and that’s the goal here. So I certainly wouldn’t say to dismiss the toxicities, but if we do have a chance to increase cures, I think we need to be mindful, but not slow going into these things.

Heather A. Wakelee, MD: No, but the trials are accruing and I just think we need to be cautious. I mean in small cell I think there were a lot of people who assumed that the maintenance was going to be a positive trial and it wasn’t, right? So we can’t always assume that it’s going to be better.

Mark A. Socinski, MD: We shouldn’t be swayed by the old saying, you know, “Don’t confuse me with the data, I know what I’m doing.”

Transcript Edited for Clarity
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