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Immunotherapy in NSCLC: Audience Q&A

Panelists: Leora Horn, MD, MSc, FRCPC, Vanderbilt University Medical Center; Edward B. Garon, MD, David Geffen School of Medicine at UCLA; Thomas E. Stinchcombe, MD, Duke Cancer Institute
Published: Tuesday, Oct 16, 2018



Transcript: 

Leora Horn, MD, MSc, FRCPC: That actually leads us to review some of the questions that have been submitted by our audience during the discussion. A biomarker question came up first. What’s the best biomarker for predicting sensitivity for a checkpoint inhibitor? What are you testing? What do you recommend we should tell people out in the community? What should be tested? And even thinking one step forward, my question to you is, what’s coming? What’s next, beyond what is being tested now?

Edward B. Garon, MD: The first half of that question is easy for me to answer. There are only 2 approved biomarkers for these therapies: PD-L1 [programmed cell death ligand 1] expression and MSI [microsatellite instability]. We don’t really see MSI-high status very much in the lungs, so that makes it easier. We do have fairly robust long-term survival data. PD-L1 is probably the single biomarker that we have, to date. I think TMB [tumor mutation burden], which we’ve already addressed, is very intriguing. It clearly correlates with progression-free survival, but it is going to have a whole host of challenges.

There are a lot of very interesting scientific biomarkers, although some of them seem a bit hard to imagine. There are thoughts about where the T cells would be. But, of course, we tend to have needle biopsies. Sometimes we even have FNAs [fine-needle aspirations], which are going to make it extraordinarily difficult to make any assessment. The microbiome has been an area of much investigation, but are all of our patients going to be reaching into the toilet to send something in? Maybe. It depends on the strength of the data. The tremendous amount of work in biomarkers is interesting. Hopefully it will give us better biomarkers. It will certainly give us a better scientific understanding.

Leora Horn, MD, MSc, FRCPC: Do you think it matters which PD-L1 assay you use?

Thomas E. Stinchcombe, MD: We generally use a Merck assay because it’s associated with reimbursement. Outside of the atezolizumab one, it looks at the tumor cells and infiltrating cells. There’s more correlation, but I generally just use the Merck assay out of simplicity.

Leora Horn, MD, MSc, FRCPC: And that’s the 22C3?

Thomas E. Stinchcombe, MD: It is the 22C3.

Leora Horn, MD, MSc, FRCPC: Tom, what are the options for treatment when a patient progresses after 8 months of osimertinib? Maybe I’ll expand on that question. What if it was alectinib or they were ROS1-positive and on crizotinib? What are you recommending for your patients?

Thomas E. Stinchcombe, MD: I try and rebiopsy these patients to make sure there’s not a small cell transformation or signal of activation of mechanism of resistance. Assuming that I don’t find one that I can easily target, I think your options would be to use platinum/pemetrexed or carboplatin, paclitaxel, bevacizumab, and atezolizumab. I’ve not used single-agent immunotherapy in this patient population, in large part due to Eddie’s work.

Leora Horn, MD, MSc, FRCPC: This is not a group of patients that does well with single-agent therapy?

Edward B. Garon, MD: No, it is not. I guess if you prove that the hypothesis is disastrously wrong, you still prove something.

Leora Horn, MD, MSc, FRCPC: Absolutely. One of the other questions that came in is on something that we really didn’t discuss before. What’s your experience with immunotherapy in small cell lung cancer? Maybe I can answer that one. Right now, nivolumab is approved in the third-line setting. There are not a lot of patients with small cell disease who get to third-line therapy. We just had data from IMpower133 that compared carboplatin and etoposide with or without atezolizumab. That has been our first positive study in several years in small cell lung cancer. There was an improvement in overall survival, although the response wasn’t higher. It’s hard to improve on a 60% to 70% response, but hopefully when it is approved I think that is a regimen that I’m going to start using in the first-line for stage IV disease. Is there any other data that you’ve seen that’s exciting or is out there?

Thomas E. Stinchcombe, MD: I think that’s the game-changer in small cell lung cancer because we’ve been stuck on platinum/etoposide for 20, 30 years now. This does show an improvement. I think we’re all interested in the nivolumab/ipilimumab combination. That obviously has a bit more toxicity. I think single-agent nivolumab has a response rate around 10% to 12%, so it’s modest activity but those responses are durable.

I hope this is just the beginning of immunotherapy. There are a number of trials—maintenance trials and other combination trials—that are maturing right now. Hopefully we’ll get those results in the next year.

Leora Horn, MD, MSc, FRCPC: Yes, hopefully we’ll see a lot more data at next year’s ASCO [American Society of Clinical Oncology] Annual Meeting with these drugs. Is there anything different that you’re doing or looking forward to seeing?

Edward B. Garon, MD: No, I was looking forward to having approval for the addition of atezolizumab, because, again, this is a place where we really haven’t had advances in a long time. I think it’ll be exciting to have something different to offer from what we’ve had, which has obviously been associated with a good response rate but not great long-term outcomes.

Leora Horn, MD, MSc, FRCPC: Absolutely. Another question that came in is, for a newly diagnosed patient, are you seeing an increase in the use of NGS [next-generation sequencing]? In cases where single gene tests must be done sequentially, what’s your preferred priority? What are you doing?

Edward B. Garon, MD: Regarding NGS, I don’t know that I’ve seen a huge upswing lately. The big question, again, goes back to TMB. You’re going to need to get NGS, probably even at centralized laboratories, if we’re going to incorporate that into our standard practice. Again, we don’t like to keep going back into the block to get the slides. It wastes tissue, which is, of course, very valuable for the patient’s care. We have been very reluctant to do anything that’s going to be sequential. We want to get as much information as we can in one swoop.

Leora Horn, MD, MSc, FRCPC: We know that the NCCN and other groups recognize and sort of brought our multiplex testing upfront, so you don’t waste that time. Tom, durvalumab maintenance is not available. Do you substitute?

Thomas E. Stinchcombe, MD: Personally, I don’t substitute; nor would I use chemotherapy consolidation. I think we’ve been down that road before. It didn’t really benefit our patients and it is associated with toxicity. I think durvalumab is still the one and only standard of care.

Leora Horn, MD, MSc, FRCPC: Related to chemotherapy consolidation, what do you do if a patient gets chemoradiotherapy with weekly paclitaxel and carboplatin? A lot of people believe that you should be getting systemic doses of a platinum doublet. Where does durvalumab fit in, and what are you doing?

Thomas E. Stinchcombe, MD: I’ve struggled with this question too. Historically, I gave weekly chemoradiation in the 2 cycles of paclitaxel and carboplatin with the understanding that there’s limited benefit. Now I’ve just been using paclitaxel and carboplatin with radiation and am quickly transitioning to durvalumab, trying to get within that 42-day window at this point.

Leora Horn, MD, MSc, FRCPC: Are you doing a similar thing?

Edward B. Garon, MD: Correct.

Leora Horn, MD, MSc, FRCPC: I find that for a lot of the patients, if you can give cisplatin/etoposide, give it. Those who got paclitaxel and carboplatin are often not the patients who can even tolerate paclitaxel and carboplatin.

That actually brings us to the top of the hour. Thank you both for an excellent discussion. We hope that you found the information to be valuable for your clinical practice. Thank you for watching OncLive® News Network.

Transcript Edited for Clarity 
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Transcript: 

Leora Horn, MD, MSc, FRCPC: That actually leads us to review some of the questions that have been submitted by our audience during the discussion. A biomarker question came up first. What’s the best biomarker for predicting sensitivity for a checkpoint inhibitor? What are you testing? What do you recommend we should tell people out in the community? What should be tested? And even thinking one step forward, my question to you is, what’s coming? What’s next, beyond what is being tested now?

Edward B. Garon, MD: The first half of that question is easy for me to answer. There are only 2 approved biomarkers for these therapies: PD-L1 [programmed cell death ligand 1] expression and MSI [microsatellite instability]. We don’t really see MSI-high status very much in the lungs, so that makes it easier. We do have fairly robust long-term survival data. PD-L1 is probably the single biomarker that we have, to date. I think TMB [tumor mutation burden], which we’ve already addressed, is very intriguing. It clearly correlates with progression-free survival, but it is going to have a whole host of challenges.

There are a lot of very interesting scientific biomarkers, although some of them seem a bit hard to imagine. There are thoughts about where the T cells would be. But, of course, we tend to have needle biopsies. Sometimes we even have FNAs [fine-needle aspirations], which are going to make it extraordinarily difficult to make any assessment. The microbiome has been an area of much investigation, but are all of our patients going to be reaching into the toilet to send something in? Maybe. It depends on the strength of the data. The tremendous amount of work in biomarkers is interesting. Hopefully it will give us better biomarkers. It will certainly give us a better scientific understanding.

Leora Horn, MD, MSc, FRCPC: Do you think it matters which PD-L1 assay you use?

Thomas E. Stinchcombe, MD: We generally use a Merck assay because it’s associated with reimbursement. Outside of the atezolizumab one, it looks at the tumor cells and infiltrating cells. There’s more correlation, but I generally just use the Merck assay out of simplicity.

Leora Horn, MD, MSc, FRCPC: And that’s the 22C3?

Thomas E. Stinchcombe, MD: It is the 22C3.

Leora Horn, MD, MSc, FRCPC: Tom, what are the options for treatment when a patient progresses after 8 months of osimertinib? Maybe I’ll expand on that question. What if it was alectinib or they were ROS1-positive and on crizotinib? What are you recommending for your patients?

Thomas E. Stinchcombe, MD: I try and rebiopsy these patients to make sure there’s not a small cell transformation or signal of activation of mechanism of resistance. Assuming that I don’t find one that I can easily target, I think your options would be to use platinum/pemetrexed or carboplatin, paclitaxel, bevacizumab, and atezolizumab. I’ve not used single-agent immunotherapy in this patient population, in large part due to Eddie’s work.

Leora Horn, MD, MSc, FRCPC: This is not a group of patients that does well with single-agent therapy?

Edward B. Garon, MD: No, it is not. I guess if you prove that the hypothesis is disastrously wrong, you still prove something.

Leora Horn, MD, MSc, FRCPC: Absolutely. One of the other questions that came in is on something that we really didn’t discuss before. What’s your experience with immunotherapy in small cell lung cancer? Maybe I can answer that one. Right now, nivolumab is approved in the third-line setting. There are not a lot of patients with small cell disease who get to third-line therapy. We just had data from IMpower133 that compared carboplatin and etoposide with or without atezolizumab. That has been our first positive study in several years in small cell lung cancer. There was an improvement in overall survival, although the response wasn’t higher. It’s hard to improve on a 60% to 70% response, but hopefully when it is approved I think that is a regimen that I’m going to start using in the first-line for stage IV disease. Is there any other data that you’ve seen that’s exciting or is out there?

Thomas E. Stinchcombe, MD: I think that’s the game-changer in small cell lung cancer because we’ve been stuck on platinum/etoposide for 20, 30 years now. This does show an improvement. I think we’re all interested in the nivolumab/ipilimumab combination. That obviously has a bit more toxicity. I think single-agent nivolumab has a response rate around 10% to 12%, so it’s modest activity but those responses are durable.

I hope this is just the beginning of immunotherapy. There are a number of trials—maintenance trials and other combination trials—that are maturing right now. Hopefully we’ll get those results in the next year.

Leora Horn, MD, MSc, FRCPC: Yes, hopefully we’ll see a lot more data at next year’s ASCO [American Society of Clinical Oncology] Annual Meeting with these drugs. Is there anything different that you’re doing or looking forward to seeing?

Edward B. Garon, MD: No, I was looking forward to having approval for the addition of atezolizumab, because, again, this is a place where we really haven’t had advances in a long time. I think it’ll be exciting to have something different to offer from what we’ve had, which has obviously been associated with a good response rate but not great long-term outcomes.

Leora Horn, MD, MSc, FRCPC: Absolutely. Another question that came in is, for a newly diagnosed patient, are you seeing an increase in the use of NGS [next-generation sequencing]? In cases where single gene tests must be done sequentially, what’s your preferred priority? What are you doing?

Edward B. Garon, MD: Regarding NGS, I don’t know that I’ve seen a huge upswing lately. The big question, again, goes back to TMB. You’re going to need to get NGS, probably even at centralized laboratories, if we’re going to incorporate that into our standard practice. Again, we don’t like to keep going back into the block to get the slides. It wastes tissue, which is, of course, very valuable for the patient’s care. We have been very reluctant to do anything that’s going to be sequential. We want to get as much information as we can in one swoop.

Leora Horn, MD, MSc, FRCPC: We know that the NCCN and other groups recognize and sort of brought our multiplex testing upfront, so you don’t waste that time. Tom, durvalumab maintenance is not available. Do you substitute?

Thomas E. Stinchcombe, MD: Personally, I don’t substitute; nor would I use chemotherapy consolidation. I think we’ve been down that road before. It didn’t really benefit our patients and it is associated with toxicity. I think durvalumab is still the one and only standard of care.

Leora Horn, MD, MSc, FRCPC: Related to chemotherapy consolidation, what do you do if a patient gets chemoradiotherapy with weekly paclitaxel and carboplatin? A lot of people believe that you should be getting systemic doses of a platinum doublet. Where does durvalumab fit in, and what are you doing?

Thomas E. Stinchcombe, MD: I’ve struggled with this question too. Historically, I gave weekly chemoradiation in the 2 cycles of paclitaxel and carboplatin with the understanding that there’s limited benefit. Now I’ve just been using paclitaxel and carboplatin with radiation and am quickly transitioning to durvalumab, trying to get within that 42-day window at this point.

Leora Horn, MD, MSc, FRCPC: Are you doing a similar thing?

Edward B. Garon, MD: Correct.

Leora Horn, MD, MSc, FRCPC: I find that for a lot of the patients, if you can give cisplatin/etoposide, give it. Those who got paclitaxel and carboplatin are often not the patients who can even tolerate paclitaxel and carboplatin.

That actually brings us to the top of the hour. Thank you both for an excellent discussion. We hope that you found the information to be valuable for your clinical practice. Thank you for watching OncLive® News Network.

Transcript Edited for Clarity 
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Community Practice Connections™: Oncology Best Practice™ Decision Points in Advanced NSCLC: Assessing Treatment Options Beyond Disease ProgressionNov 30, 20181.0
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