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Pembrolizumab as Treatment for Oligometastatic 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: 

Mark A. Socinski, MD: Suresh, we received data at the World Conference on Lung Cancer [WCLC] 2018 Annual Meeting looking at this cohort of patients who were oligometastatic. There was a phase II study using pembrolizumab along with locally ablative therapies. Could you tell us about that?

Suresh Senan, MRCP, FRCR, PhD: It’s a nice follow-up to the study that Dr. Daniel Gomez published in Lancet Oncology about 2 years ago, showing that when you give locally ablative therapy in a randomized fashion, you prolong the progression-free survival significantly—about 3 times as much. The Independent Data Monitoring Committees [IDMC] closed that study down. Yesterday at the ASTRO 2018 Annual Meeting, Dr. Daniel Gomez present this data regarding the overall survival benefit. There’s something to it. What this study did at the World Congress was look to see where they administer I-O—in this case, pembrolizumab—after locally ablative therapy, and if it would be feasible. They tried to see whether they could extend the PFS from 6 months to 11 months. They showed an impressive PFS, of around 19 months; however, there are some caveats. Firstly, about 60% of patients had oligorecurrence, which meant they had metachronous oligometastases—whereas in Dr. Daniel Gomez’s trial, about 92% had synchronous metastases, which we’re thinking about; you choose a subgroup which tends to do very well. Secondly, 60% had 1 metastases and another 30% had 2. If you take these groups—metachronous in 1 or 2 sites—you tend to do well.

Today at the ASTRO meeting, the results of the randomized COMET trial regarding oligorecurrences show that giving stereotactic radiotherapy as the standard of care results in a PFS of 6 months and an OS of about 13 months. It shows that pembrolizumab after locally ablative therapy is feasible since randomized evidence is adequately powering trials. We should be looking now at the patients with synchronous metastases, perhaps up to 4, as was done in Dr. Daniel Gomez’s trial. There’s room for good prospective trials. I see this as an indicator that it’s feasible.

Mark A. Socinski, MD: What do you think is going on there from a mechanism point of view?

Suresh Senan, MRCP, FRCR, PhD: I think 1+1 is 2. I’m not sure about abscopal effects or stimulating the radiation.

Mark A. Socinski, MD: We hear a lot about the abscopal effect. We don’t see it very often.

Suresh Senan, MRCP, FRCR, PhD: At this point in time we should give the radiotherapy in locally ablative doses that we want to give to the sustained control. The COMET trial shows that you only have about 70% local control rates at these sites we administer stereotactic ablative radiotherapy [SABR] to; it’s not 100% or 90%. If a patient is referred to me in this context, I would give an optimal SABR dose that’s safe, and leave it to the systemic therapy to continue.

Mark A. Socinski, MD: Do we all agree?

Thomas E. Stinchcombe, MD: Yes. The critical thing is, a lot of these trials have carefully selected patients, so they’re somewhat hard to interpret.

Transcript Edited for Clarity 

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Transcript: 

Mark A. Socinski, MD: Suresh, we received data at the World Conference on Lung Cancer [WCLC] 2018 Annual Meeting looking at this cohort of patients who were oligometastatic. There was a phase II study using pembrolizumab along with locally ablative therapies. Could you tell us about that?

Suresh Senan, MRCP, FRCR, PhD: It’s a nice follow-up to the study that Dr. Daniel Gomez published in Lancet Oncology about 2 years ago, showing that when you give locally ablative therapy in a randomized fashion, you prolong the progression-free survival significantly—about 3 times as much. The Independent Data Monitoring Committees [IDMC] closed that study down. Yesterday at the ASTRO 2018 Annual Meeting, Dr. Daniel Gomez present this data regarding the overall survival benefit. There’s something to it. What this study did at the World Congress was look to see where they administer I-O—in this case, pembrolizumab—after locally ablative therapy, and if it would be feasible. They tried to see whether they could extend the PFS from 6 months to 11 months. They showed an impressive PFS, of around 19 months; however, there are some caveats. Firstly, about 60% of patients had oligorecurrence, which meant they had metachronous oligometastases—whereas in Dr. Daniel Gomez’s trial, about 92% had synchronous metastases, which we’re thinking about; you choose a subgroup which tends to do very well. Secondly, 60% had 1 metastases and another 30% had 2. If you take these groups—metachronous in 1 or 2 sites—you tend to do well.

Today at the ASTRO meeting, the results of the randomized COMET trial regarding oligorecurrences show that giving stereotactic radiotherapy as the standard of care results in a PFS of 6 months and an OS of about 13 months. It shows that pembrolizumab after locally ablative therapy is feasible since randomized evidence is adequately powering trials. We should be looking now at the patients with synchronous metastases, perhaps up to 4, as was done in Dr. Daniel Gomez’s trial. There’s room for good prospective trials. I see this as an indicator that it’s feasible.

Mark A. Socinski, MD: What do you think is going on there from a mechanism point of view?

Suresh Senan, MRCP, FRCR, PhD: I think 1+1 is 2. I’m not sure about abscopal effects or stimulating the radiation.

Mark A. Socinski, MD: We hear a lot about the abscopal effect. We don’t see it very often.

Suresh Senan, MRCP, FRCR, PhD: At this point in time we should give the radiotherapy in locally ablative doses that we want to give to the sustained control. The COMET trial shows that you only have about 70% local control rates at these sites we administer stereotactic ablative radiotherapy [SABR] to; it’s not 100% or 90%. If a patient is referred to me in this context, I would give an optimal SABR dose that’s safe, and leave it to the systemic therapy to continue.

Mark A. Socinski, MD: Do we all agree?

Thomas E. Stinchcombe, MD: Yes. The critical thing is, a lot of these trials have carefully selected patients, so they’re somewhat hard to interpret.

Transcript Edited for Clarity 
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