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Treatment Options for mNSCLC After Progression

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: Monday, Apr 01, 2019



Transcript: 

Mark A. Socinski, MD: And so I think that that’s true. So if we’ve done that—and I’m not going to ask people what they used to do for third-line therapy, because now we call it a second line—so you use up your options, Leora, in the first-line setting, chemo and immunotherapy. And let’s just take the group of patients that already received a platinum doublet plus one of the I/O [immuno-oncology] agents, plus or minus BEV [bevacizumab]. You know all that sort of stuff. What do you do next?

Leora Horn, MD, MSc, FRCPC: So outside of a clinical trial?

Mark A. Socinski, MD: Yes.

Leora Horn, MD, MSc, FRCPC: So I think we’re back to using docetaxel with or without ramucirumab. And years ago I remember Heather saying to me, because I was complaining about docetaxel, that she never gives anyone 75. She does 60 or she does 36 weekly.

Mark A. Socinski, MD: Yeah, me, too.

Leora Horn, MD, MSc, FRCPC: And I adopted that. So I will give docetaxel, often 60, and I do have several patients who I’m giving ramucirumab with docetaxel. It’s the old second-line DEK in second-line because it’s no longer third-line again.

Mark A. Socinski, MD: Yeah, and the option there is that it appears to be perfectly safe in the squamous population also.

Leora Horn, MD, MSc, FRCPC: Right.

Mark A. Socinski, MD: So it has a wider applicability. Other comments about second line?

Heather A. Wakelee, MD: No. I’m just going to back up a little bit. I use docetaxel in that setting, but I almost always give it weekly—either 35 or 37 mg/m2 if they’re fit, and I’ll give 2 weeks on and a week off, or I’ll do 30.

Mark A. Socinski, MD: No, I do that too, and I just do a day 1 and 8, q21-day, every 21 days schedule, because I give the ramucirumab, but I don’t know that there’s any clinical trial data using ramucirumab with a weekly dose.

Heather A. Wakelee, MD: Right. They’re talking about doing a study but it hasn’t been done.

Mark A. Socinski, MD: Okay.

Mohammad Jahanzeb, MD: Well while they’re at doing a study, I hope they choose different cytotoxic agents also.

Mohammad Jahanzeb, MD: I’ll save docetaxel for fifth or sixth line.

Heather A. Wakelee, MD: Do you like gemcitabine more?

Mohammad Jahanzeb, MD: Yes, and vinorelbine, and irinotecan.

Heather A. Wakelee, MD: Yeah, irinotecan, I’ll use that.

Mohammad Jahanzeb, MD: So I have 3 other drugs that I go to before I go to docetaxel. And if I ever go there, I give a weekly taxane, weekly Taxol rather—paclitaxel rather than going to docetaxel—because I’ve given a lot of docetaxel in my lifetime and given actually a lot of lectures about docetaxel. But these new immunotherapy trials, one thing that they cemented in me—because all of them used that as the control arm—is that the grade 3 tox, the grade 3/4 toxicity is not the 50%. And once I realized that it’s not the 50%, I just couldn’t do it after that.

Heather A. Wakelee, MD: But this is the 75.

Mohammad Jahanzeb, MD: That’s at 75, yeah. But what I’m saying is there are other options. There are other cytotoxic drugs.

John V. Heymach, MD, PhD: Yeah. You know but in the third-line setting, so I certainly agree that docetaxel is not a perfect drug, and it would be interesting to see different combinations with ramucirumab. I think people sometimes discount the potential benefits of ramucirumab a little too easily. The hazard ratio is less than .8. That adds real efficacy. So I do use ramucirumab frequently when I’m combining it with docetaxel.

When you go back and look at the old vinorelbine data or the ifosfamide data, when docetaxel was first approved, the Facella study, because even though I was using it commonly, the objective response rate for single-agent vinorelbine was actually less than 1% in the neoadjuvant study.

Mohammad Jahanzeb, MD: Yeah, it was 1 respondent, and that’s 30 years and more disservice to vinorelbine used.

John V. Heymach, MD, PhD: But even if you go to other studies, like the Elvis study, for example, and others, clearly single-agent response rates are very low. Now I personally think we may be underestimating the benefit. You may be getting more stable disease or minor shrinkage in different cases.

Mohammad Jahanzeb, MD: Yes. Because in the same study, the docetaxel response rate was 8%.

John V. Heymach, MD, PhD: Right. Well and I think most studies now settle out in that 8%-to-13% range for the single-agent docetaxel. But I think the real benefits are going to be with either immunotherapy or other targeted agents in combination. And I don’t know that we know for sure docetaxel is a good partner with immunotherapy. So it would be interesting to explore things like vinorelbine and gemcitabine. There’s a little bit of data that gemcitabine may preferentially target some of these immunosuppressive myeloid cells, for example. It would be nice to bring back some of those other agents and see if they are better partners with immunotherapy.

Leora Horn, MD, MSc, FRCPC: There is a trial looking at platinum, gemcitabine, and one of the—I don’t remember which checkpoint inhibitor, but there is a trial that is looking at that data.

Heather A. Wakelee, MD: Yeah, it’s the Novartis study dealing with the PDR001; that’s one of the arms that got cited. There are probably others.

Mark A. Socinski, MD: So we’ve talked about the chemo plus I/O. I’m going to ask Jarushka. What do you do after pembro [pembrolizumab] monotherapy, those high expressors?

John V. Heymach, MD, PhD: Yeah. Well I think the great thing after pembro monotherapy is you’ve still got your good old-fashioned platinum doublet to go to. And I certainly feel that in that patient population if I can give the monotherapy, that is a very strong reason why I prefer it, because I have a good second-line regimen that I know has great data to support it. So I think if you can, you should.

Transcript Edited for Clarity

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Transcript: 

Mark A. Socinski, MD: And so I think that that’s true. So if we’ve done that—and I’m not going to ask people what they used to do for third-line therapy, because now we call it a second line—so you use up your options, Leora, in the first-line setting, chemo and immunotherapy. And let’s just take the group of patients that already received a platinum doublet plus one of the I/O [immuno-oncology] agents, plus or minus BEV [bevacizumab]. You know all that sort of stuff. What do you do next?

Leora Horn, MD, MSc, FRCPC: So outside of a clinical trial?

Mark A. Socinski, MD: Yes.

Leora Horn, MD, MSc, FRCPC: So I think we’re back to using docetaxel with or without ramucirumab. And years ago I remember Heather saying to me, because I was complaining about docetaxel, that she never gives anyone 75. She does 60 or she does 36 weekly.

Mark A. Socinski, MD: Yeah, me, too.

Leora Horn, MD, MSc, FRCPC: And I adopted that. So I will give docetaxel, often 60, and I do have several patients who I’m giving ramucirumab with docetaxel. It’s the old second-line DEK in second-line because it’s no longer third-line again.

Mark A. Socinski, MD: Yeah, and the option there is that it appears to be perfectly safe in the squamous population also.

Leora Horn, MD, MSc, FRCPC: Right.

Mark A. Socinski, MD: So it has a wider applicability. Other comments about second line?

Heather A. Wakelee, MD: No. I’m just going to back up a little bit. I use docetaxel in that setting, but I almost always give it weekly—either 35 or 37 mg/m2 if they’re fit, and I’ll give 2 weeks on and a week off, or I’ll do 30.

Mark A. Socinski, MD: No, I do that too, and I just do a day 1 and 8, q21-day, every 21 days schedule, because I give the ramucirumab, but I don’t know that there’s any clinical trial data using ramucirumab with a weekly dose.

Heather A. Wakelee, MD: Right. They’re talking about doing a study but it hasn’t been done.

Mark A. Socinski, MD: Okay.

Mohammad Jahanzeb, MD: Well while they’re at doing a study, I hope they choose different cytotoxic agents also.

Mohammad Jahanzeb, MD: I’ll save docetaxel for fifth or sixth line.

Heather A. Wakelee, MD: Do you like gemcitabine more?

Mohammad Jahanzeb, MD: Yes, and vinorelbine, and irinotecan.

Heather A. Wakelee, MD: Yeah, irinotecan, I’ll use that.

Mohammad Jahanzeb, MD: So I have 3 other drugs that I go to before I go to docetaxel. And if I ever go there, I give a weekly taxane, weekly Taxol rather—paclitaxel rather than going to docetaxel—because I’ve given a lot of docetaxel in my lifetime and given actually a lot of lectures about docetaxel. But these new immunotherapy trials, one thing that they cemented in me—because all of them used that as the control arm—is that the grade 3 tox, the grade 3/4 toxicity is not the 50%. And once I realized that it’s not the 50%, I just couldn’t do it after that.

Heather A. Wakelee, MD: But this is the 75.

Mohammad Jahanzeb, MD: That’s at 75, yeah. But what I’m saying is there are other options. There are other cytotoxic drugs.

John V. Heymach, MD, PhD: Yeah. You know but in the third-line setting, so I certainly agree that docetaxel is not a perfect drug, and it would be interesting to see different combinations with ramucirumab. I think people sometimes discount the potential benefits of ramucirumab a little too easily. The hazard ratio is less than .8. That adds real efficacy. So I do use ramucirumab frequently when I’m combining it with docetaxel.

When you go back and look at the old vinorelbine data or the ifosfamide data, when docetaxel was first approved, the Facella study, because even though I was using it commonly, the objective response rate for single-agent vinorelbine was actually less than 1% in the neoadjuvant study.

Mohammad Jahanzeb, MD: Yeah, it was 1 respondent, and that’s 30 years and more disservice to vinorelbine used.

John V. Heymach, MD, PhD: But even if you go to other studies, like the Elvis study, for example, and others, clearly single-agent response rates are very low. Now I personally think we may be underestimating the benefit. You may be getting more stable disease or minor shrinkage in different cases.

Mohammad Jahanzeb, MD: Yes. Because in the same study, the docetaxel response rate was 8%.

John V. Heymach, MD, PhD: Right. Well and I think most studies now settle out in that 8%-to-13% range for the single-agent docetaxel. But I think the real benefits are going to be with either immunotherapy or other targeted agents in combination. And I don’t know that we know for sure docetaxel is a good partner with immunotherapy. So it would be interesting to explore things like vinorelbine and gemcitabine. There’s a little bit of data that gemcitabine may preferentially target some of these immunosuppressive myeloid cells, for example. It would be nice to bring back some of those other agents and see if they are better partners with immunotherapy.

Leora Horn, MD, MSc, FRCPC: There is a trial looking at platinum, gemcitabine, and one of the—I don’t remember which checkpoint inhibitor, but there is a trial that is looking at that data.

Heather A. Wakelee, MD: Yeah, it’s the Novartis study dealing with the PDR001; that’s one of the arms that got cited. There are probably others.

Mark A. Socinski, MD: So we’ve talked about the chemo plus I/O. I’m going to ask Jarushka. What do you do after pembro [pembrolizumab] monotherapy, those high expressors?

John V. Heymach, MD, PhD: Yeah. Well I think the great thing after pembro monotherapy is you’ve still got your good old-fashioned platinum doublet to go to. And I certainly feel that in that patient population if I can give the monotherapy, that is a very strong reason why I prefer it, because I have a good second-line regimen that I know has great data to support it. So I think if you can, you should.

Transcript Edited for Clarity
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