ONCAlert | Upfront Therapy for mRCC

Case 2: Treatment Considerations in Stage IV NSCLC

Targeted Oncology
Published Online:8:10 PM, Wed September 19, 2018


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Paul K. Paik, MD:
It sounds like there’s consensus that we would do platinum/pemetrexed/pembrolizumab in this case. The trial was structured to give 4 cycles of platinum/pemetrexed. Then, there was the option for maintenance pemetrexed. Are you guys doing maintenance pemetrexed with the pembrolizumab, or are you dropping the pemetrexed?

Anne S. Tsao, MD: I am. It’s up to, I think, 35 cycles. So, I do that, but there have been a couple of cases where I did drop the pemetrexed because of refractory anemia. I just continue the pembrolizumab out.

Benjamin P. Levy, MD: Yes. For this patient, I would give 4 cycles of triplet therapy and drop the carboplatin. I’d probably continue the pemetrexed and the pembrolizumab—PEM-squared. Generally, there may be some synergy with these 2 drugs that we’re obviously seeing in the triplet regimen. But maybe it’s really those 2 drugs, put together, that cause or drive this benefit. We don’t know. So, for this patient, that’s what I would do. I would do 3 cycles followed by maintenance pemetrexed indefinitely, until disease progression or bad tolerability to the drugs.

Anne S. Tsao, MD: I think it’s really about the toxicity profile and how the patient is looking. That really drives my decision. I try to keep pembrolizumab as a preference, and I’ll usually drop the pemetrexed if I have to drop a therapy.

Benjamin P. Levy, MD: What about at Memorial Sloan Kettering Cancer Center?

Paul K. Paik, MD: We were holdouts based on the KEYNOTE-021 cohort G data. We did not put that into play. But, with KEYNOTE-189, we’re routinely doing this. I tend to agree. The trial was structured where maintenance pemetrexed was allowed. Some patients had some amount of this. You can’t discount the fact that there is some interaction between that and immunotherapy. If anything, the chemoimmunotherapy era tells us that’s the case. So, we try to continue it for as long as possible.

The last question that I want to ask here, in this case, in the time that remains, is something that’s also clinically relevant. We have a very symptomatic patient here. What if the patient’s PD-L1 [programmed-cell death ligand 1] expression was high? What if it was 70% or 80%? From the KEYNOTE-024 data, we know that single-agent pembrolizumab is an option. How would you give that? Would you give chemoimmunotherapy?

Anne S. Tsao, MD: That’s the big question right now, right? What do you do for the high PD-L1 expressers? Honestly, if somebody is asymptomatic with tumor disease burden that is not imminently threatened, you can take the time to give single-agent pembrolizumab. I often think that the monotherapies tend to not debulk the tumor as quickly as when you use a triplet regimen. But, in this case, we have a patient who is symptomatic. This patient appears to be ill. She has a good enough performance status. If she can tolerate the triplet regimen, and just because of the symptoms, I would actually go with the triplet regimen. The triplet regimen has the highest response rates in the PD-L1–high population when you look at the data from KEYNOTE-189.

Benjamin P. Levy, MD: I agree. I think that treatment decisions have to be individualized. If a patient’s PD-L1 is greater than 50%, you have the option of single-agent pembrolizumab versus triplet therapy. The benefit was across the board. The hazard ratio is a little more robust for the triplet regimen in the patients who have a PD-L1 that is greater than 50%. In KEYNOTE-024, obviously everyone was greater than 50%. But, I think it’s individualized. If I have a symptomatic patient, maybe I would use triplet therapy. If they’re not so symptomatic and I think I’ve got a little time, I’d just give the patient single-agent pembrolizumab.

Anne S. Tsao, MD: I had a 92-year-old man come into my clinic the other day. He’s 80% PD-L1–positive. So, I went with pembrolizumab, alone.

Paul K. Paik, MD: I think that’s what I would have done. I’d like to close this case by stating that it’s a great time, right now, in the first-line setting for non–small cell lung cancer. There are some things that we have to work out, but the options that we have are options that have really moved the bar, in terms of overall survival. So, I think there’s a great deal of optimism moving forward.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Paul K. Paik, MD:
It sounds like there’s consensus that we would do platinum/pemetrexed/pembrolizumab in this case. The trial was structured to give 4 cycles of platinum/pemetrexed. Then, there was the option for maintenance pemetrexed. Are you guys doing maintenance pemetrexed with the pembrolizumab, or are you dropping the pemetrexed?

Anne S. Tsao, MD: I am. It’s up to, I think, 35 cycles. So, I do that, but there have been a couple of cases where I did drop the pemetrexed because of refractory anemia. I just continue the pembrolizumab out.

Benjamin P. Levy, MD: Yes. For this patient, I would give 4 cycles of triplet therapy and drop the carboplatin. I’d probably continue the pemetrexed and the pembrolizumab—PEM-squared. Generally, there may be some synergy with these 2 drugs that we’re obviously seeing in the triplet regimen. But maybe it’s really those 2 drugs, put together, that cause or drive this benefit. We don’t know. So, for this patient, that’s what I would do. I would do 3 cycles followed by maintenance pemetrexed indefinitely, until disease progression or bad tolerability to the drugs.

Anne S. Tsao, MD: I think it’s really about the toxicity profile and how the patient is looking. That really drives my decision. I try to keep pembrolizumab as a preference, and I’ll usually drop the pemetrexed if I have to drop a therapy.

Benjamin P. Levy, MD: What about at Memorial Sloan Kettering Cancer Center?

Paul K. Paik, MD: We were holdouts based on the KEYNOTE-021 cohort G data. We did not put that into play. But, with KEYNOTE-189, we’re routinely doing this. I tend to agree. The trial was structured where maintenance pemetrexed was allowed. Some patients had some amount of this. You can’t discount the fact that there is some interaction between that and immunotherapy. If anything, the chemoimmunotherapy era tells us that’s the case. So, we try to continue it for as long as possible.

The last question that I want to ask here, in this case, in the time that remains, is something that’s also clinically relevant. We have a very symptomatic patient here. What if the patient’s PD-L1 [programmed-cell death ligand 1] expression was high? What if it was 70% or 80%? From the KEYNOTE-024 data, we know that single-agent pembrolizumab is an option. How would you give that? Would you give chemoimmunotherapy?

Anne S. Tsao, MD: That’s the big question right now, right? What do you do for the high PD-L1 expressers? Honestly, if somebody is asymptomatic with tumor disease burden that is not imminently threatened, you can take the time to give single-agent pembrolizumab. I often think that the monotherapies tend to not debulk the tumor as quickly as when you use a triplet regimen. But, in this case, we have a patient who is symptomatic. This patient appears to be ill. She has a good enough performance status. If she can tolerate the triplet regimen, and just because of the symptoms, I would actually go with the triplet regimen. The triplet regimen has the highest response rates in the PD-L1–high population when you look at the data from KEYNOTE-189.

Benjamin P. Levy, MD: I agree. I think that treatment decisions have to be individualized. If a patient’s PD-L1 is greater than 50%, you have the option of single-agent pembrolizumab versus triplet therapy. The benefit was across the board. The hazard ratio is a little more robust for the triplet regimen in the patients who have a PD-L1 that is greater than 50%. In KEYNOTE-024, obviously everyone was greater than 50%. But, I think it’s individualized. If I have a symptomatic patient, maybe I would use triplet therapy. If they’re not so symptomatic and I think I’ve got a little time, I’d just give the patient single-agent pembrolizumab.

Anne S. Tsao, MD: I had a 92-year-old man come into my clinic the other day. He’s 80% PD-L1–positive. So, I went with pembrolizumab, alone.

Paul K. Paik, MD: I think that’s what I would have done. I’d like to close this case by stating that it’s a great time, right now, in the first-line setting for non–small cell lung cancer. There are some things that we have to work out, but the options that we have are options that have really moved the bar, in terms of overall survival. So, I think there’s a great deal of optimism moving forward.

Transcript edited for clarity.
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