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Practice Changes for Use of Immunotherapy in NSCLC: Q&A

Panelists: Jack West, MD, Swedish Cancer Institute; Gregory J. Riely, MD, PhD, Memorial Sloan Kettering Cancer Center; Jared Weiss, MD, UNC School of Medicine; Charu Aggarwal, MD, MPH, University of Pennsylvania Hospital
Published: Monday, Jul 23, 2018



Transcript: 

Jack West, MD: Let’s turn to some of the questions from the viewers. One is, based on all of the data that have come in, what is your treatment of choice for the patients with 1% to 49% PD-L1?

Gregory J. Riely, MD, PhD: I’ll give that patient chemotherapy plus immunotherapy. Based on where we are today, I don’t think single-agent immunotherapy is appropriate for the majority of those patients.

Charu Aggarwal, MD, MPH: Yes, I would just highlight that the hazard ratio for that group of 1% to 49% on KEYNOTE-042 was 0.9. So, there was really no difference if you gave them chemotherapy versus immunotherapy. And I think we saw clearer improvement in survival with KEYNOTE-189 and with KEYNOTE-407. So, I think it would be a chemotherapy triplet combination for me as well.

Jack West, MD: So, again, the comparator today in real-world terms is not chemotherapy alone, it’s now chemoimmunotherapy. And you do have a choice of a few different positive trial results, and I agree that histology-appropriate chemoimmunotherapy with pembrolizumab bubbles up at the top right now.

Jared Weiss, MD: I would say, though that I don’t feel a total compulsion in the 0%-to-49% group. I think it’s still legitimate to do clinical trials guaranteeing exposure to these agents in a consolidation or maintenance strategy. I think that’s actually consistent with the principles gleaned from this data. And for the patient with a relative but not absolute contraindication to immunotherapy drugs—that patient where we may have a little bit more fear, but it’s not going to totally stop us—I think it’s legitimate to reserve the immunotherapy for the second-line setting.

Jack West, MD: Now somebody asked also, does the actual agent matter? And my view is, we’ve talked about how they’re more similar than different, but I would certainly be inclined to use the agent that the trial employed, do what the data show you rather than just cavalierly presume they will be exactly the same. You agree?

Jared Weiss, MD: Yes. I think the differences that we’ve seen between these agents reflect more the populations accrued and the way the trials were designed than structural differences between the antibodies. The classic example might be the nivolumab/pembrolizumab combination where in lung cancer, you could look at this data and argue that perhaps pembrolizumab looks better. But in contrast, there’s a similar experience in head and neck cancer where you’d be arguing that nivolumab looks better. I don’t think there’s a disease-by-drug interaction. I think you just had different patients, different comparators, different trial designs.

Jack West, MD: We have a provocative question. We have data from squamous and nonsquamous. But what about a patient with large-cell neuroendocrine carcinoma? Would you use the KEYNOTE-189 approach or would you be inclined to use pembrolizumab monotherapy? Would you be inclined to do a platinum and etoposide with pembrolizumab? Which I think would be my preference.

Gregory J. Riely, MD, PhD: Yes, I think this is faith-based medicine. We have very little data to guide us here, and I’ve always followed my religion for large-cell neuroendocrine because it’s a nonsquamous entity. And so, I give pemetrexed platinum. And now in this day and age, I’ll add pembrolizumab to it as well.

Jared Weiss, MD: I feel the same way, especially if they’re TTF1-positive. Then I’m even more comfortable with the use of pemetrexed.

Charu Aggarwal, MD, MPH: I would favor an etoposide-containing regimen for a neuroendocrine histology still. I think there’s not a right or wrong answer here, but that would still be my preference.

Jack West, MD: This is one religious argument where I wouldn’t fight to the death on it. And then there’s the question of, what about a patient who progresses really rapidly, within the first 4 months or so after chemoimmunotherapy? Are we really left with chemotherapy or are we left with docetaxel with or without ramucirumab? And there are some data from the REVEL trial that suggested the patients with rapidly progressing disease may get a real benefit from ramucirumab. What would be your approach to this kind of situation, which is not going to be rare?

Jared Weiss, MD: This is the patient who should go on a clinical trial. If you have rapid progression after a use of our most active agent, going back to the well and repeating cytotoxics and thinking that you’re going to have a high probability of response stands in contrast to the data that we already have. Ideally, that trial should be at UNC.

Jack West, MD: Yes, the problem is trials are always the right answer but they aren’t universally available.

Charu Aggarwal, MD, MPH: And I would say that rapidly progressing patients are seldom good clinical trial candidates. Those are the ones who are in pain, their performance status is poor, or their labs are tanking. So, I would say that our general approach for these patients at this time would be docetaxel and ramucirumab if they’re able to receive it.

Jack West, MD: Your thoughts?

Gregory J. Riely, MD, PhD: I would use docetaxel, mostly just docetaxel.

Jared Weiss, MD: The only other thing I would add is that given the lower probability of cytotoxic response, at this point if you don’t have a trial, you need to also be at least talking to the patient about hospice and making sure that further treatment with lower probability of response is consistent with their values.

Charu Aggarwal, MD, MPH: Clinical trial or hospice, nothing in between?

Jared Weiss, MD: Well, if they’re not a good candidate, I’ll send them to Penn Medicine.

Jack West, MD: We would also love to know whether it is true that patients may do better with chemotherapy, even garden-variety chemotherapy, after immunotherapy, that we need to get some actual data on, at least prospective data.

So, we could go on forever. This has been a great discussion, and there’s going to be so much more to talk about in the coming months. We’ll have to do this again. So, this has been a great discussion, and I hope you found the information valuable to you and clinical practice. Thank you for watching OncLive® NewsNetwork.

Transcript Edited for Clarity 
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Transcript: 

Jack West, MD: Let’s turn to some of the questions from the viewers. One is, based on all of the data that have come in, what is your treatment of choice for the patients with 1% to 49% PD-L1?

Gregory J. Riely, MD, PhD: I’ll give that patient chemotherapy plus immunotherapy. Based on where we are today, I don’t think single-agent immunotherapy is appropriate for the majority of those patients.

Charu Aggarwal, MD, MPH: Yes, I would just highlight that the hazard ratio for that group of 1% to 49% on KEYNOTE-042 was 0.9. So, there was really no difference if you gave them chemotherapy versus immunotherapy. And I think we saw clearer improvement in survival with KEYNOTE-189 and with KEYNOTE-407. So, I think it would be a chemotherapy triplet combination for me as well.

Jack West, MD: So, again, the comparator today in real-world terms is not chemotherapy alone, it’s now chemoimmunotherapy. And you do have a choice of a few different positive trial results, and I agree that histology-appropriate chemoimmunotherapy with pembrolizumab bubbles up at the top right now.

Jared Weiss, MD: I would say, though that I don’t feel a total compulsion in the 0%-to-49% group. I think it’s still legitimate to do clinical trials guaranteeing exposure to these agents in a consolidation or maintenance strategy. I think that’s actually consistent with the principles gleaned from this data. And for the patient with a relative but not absolute contraindication to immunotherapy drugs—that patient where we may have a little bit more fear, but it’s not going to totally stop us—I think it’s legitimate to reserve the immunotherapy for the second-line setting.

Jack West, MD: Now somebody asked also, does the actual agent matter? And my view is, we’ve talked about how they’re more similar than different, but I would certainly be inclined to use the agent that the trial employed, do what the data show you rather than just cavalierly presume they will be exactly the same. You agree?

Jared Weiss, MD: Yes. I think the differences that we’ve seen between these agents reflect more the populations accrued and the way the trials were designed than structural differences between the antibodies. The classic example might be the nivolumab/pembrolizumab combination where in lung cancer, you could look at this data and argue that perhaps pembrolizumab looks better. But in contrast, there’s a similar experience in head and neck cancer where you’d be arguing that nivolumab looks better. I don’t think there’s a disease-by-drug interaction. I think you just had different patients, different comparators, different trial designs.

Jack West, MD: We have a provocative question. We have data from squamous and nonsquamous. But what about a patient with large-cell neuroendocrine carcinoma? Would you use the KEYNOTE-189 approach or would you be inclined to use pembrolizumab monotherapy? Would you be inclined to do a platinum and etoposide with pembrolizumab? Which I think would be my preference.

Gregory J. Riely, MD, PhD: Yes, I think this is faith-based medicine. We have very little data to guide us here, and I’ve always followed my religion for large-cell neuroendocrine because it’s a nonsquamous entity. And so, I give pemetrexed platinum. And now in this day and age, I’ll add pembrolizumab to it as well.

Jared Weiss, MD: I feel the same way, especially if they’re TTF1-positive. Then I’m even more comfortable with the use of pemetrexed.

Charu Aggarwal, MD, MPH: I would favor an etoposide-containing regimen for a neuroendocrine histology still. I think there’s not a right or wrong answer here, but that would still be my preference.

Jack West, MD: This is one religious argument where I wouldn’t fight to the death on it. And then there’s the question of, what about a patient who progresses really rapidly, within the first 4 months or so after chemoimmunotherapy? Are we really left with chemotherapy or are we left with docetaxel with or without ramucirumab? And there are some data from the REVEL trial that suggested the patients with rapidly progressing disease may get a real benefit from ramucirumab. What would be your approach to this kind of situation, which is not going to be rare?

Jared Weiss, MD: This is the patient who should go on a clinical trial. If you have rapid progression after a use of our most active agent, going back to the well and repeating cytotoxics and thinking that you’re going to have a high probability of response stands in contrast to the data that we already have. Ideally, that trial should be at UNC.

Jack West, MD: Yes, the problem is trials are always the right answer but they aren’t universally available.

Charu Aggarwal, MD, MPH: And I would say that rapidly progressing patients are seldom good clinical trial candidates. Those are the ones who are in pain, their performance status is poor, or their labs are tanking. So, I would say that our general approach for these patients at this time would be docetaxel and ramucirumab if they’re able to receive it.

Jack West, MD: Your thoughts?

Gregory J. Riely, MD, PhD: I would use docetaxel, mostly just docetaxel.

Jared Weiss, MD: The only other thing I would add is that given the lower probability of cytotoxic response, at this point if you don’t have a trial, you need to also be at least talking to the patient about hospice and making sure that further treatment with lower probability of response is consistent with their values.

Charu Aggarwal, MD, MPH: Clinical trial or hospice, nothing in between?

Jared Weiss, MD: Well, if they’re not a good candidate, I’ll send them to Penn Medicine.

Jack West, MD: We would also love to know whether it is true that patients may do better with chemotherapy, even garden-variety chemotherapy, after immunotherapy, that we need to get some actual data on, at least prospective data.

So, we could go on forever. This has been a great discussion, and there’s going to be so much more to talk about in the coming months. We’ll have to do this again. So, this has been a great discussion, and I hope you found the information valuable to you and clinical practice. Thank you for watching OncLive® NewsNetwork.

Transcript Edited for Clarity 
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