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Novel EGFR Inhibitor Combinations for NSCLC

Panelists: Joshua Bauml, MD, University of Pennsylvania; D. Ross Camidge, MD, University of Colorado School of Medicine; Robert Doebele, MD, PhD, University of Colorado School of Medicine; Benjamin Levy, MD, Johns Hopkins Sidney Kimmel Cancer Center; Zofia Piotrowska, MD, Harvard Medical School
Published: Friday, Aug 09, 2019



Transcript:

Benjamin Levy, MD: Let’s move on to some of the data we saw at ASCO [the American Society of Clinical Oncology annual meeting] today in the oral sessions. We’re trying to move the bar forward and looking at optimizing treatment for patients with EGFR-mutated lung cancer. This speaks to the heterogeneity of EGFR-mutated lung cancer. We’re starting to see signals of adding chemotherapy or antiangiogenesis drugs up front that may lead to improved outcomes. Ross, do you want to tackle abstract number 9001, which was essentially looking at gefitinib versus gefitinib plus chemotherapy, some of the data we saw last year at ASCO, in another dataset now?

D. Ross Camidge, MD: It was wonderful on several levels. One, it was the first really good data I’ve seen coming out of an Indian institution—tremendously enthusiastic and very impressive presenter. This was a home-grown study. EGFR-mutated patients, several hundred patients randomized to getting gefitinib or gefitinib plus carboplatin and pemetrexed. And it was quite dramatic. It increased the response rate. It doubled the PFS [progression-free survival] from something like 8 to 16 months, so it’s easy to figure out the hazard ratio, it’s 0.5. And it even increased overall survival [OS].

Now, with overall survival, the issue is in that setting, the ability to get next line therapy may be problematic. For example, in the control arm only 30% of people got chemotherapy. There’s an element  that you’re just stacking the deck up front. But it really makes you pause for thought. Is this something that is the best thing for our patients, recognizing that there’s an element of back to the future with this? It’s like we’re going back to chemotherapy after we said, great, you just get a pill? It really makes you think about whether you could have that discussion with a patient and say, look, there’s this data out there. OK, it was a single site, it was a big study, it was randomized, but what do you think about adding in some chemotherapy up front?

Benjamin Levy, MD: Are you ready to extrapolate and add it to osimertinib? I mean, we’ve got 2 datasets now showing that chemotherapy added to first-generation TKI [tyrosine kinase inhibitor] leads to these whopping improvements in OS that we don’t normally see. Is that a consideration right now? I know it’s not approved, but is there a patient where you may think, look, I’ve got this data with first-generation TKI showing a survival advantage, symptomatic patient, think you can tolerate, very young, would you add chemotherapy ever?

D. Ross Camidge, MD: The great thing is, so the 2 concerns are 1) it wasn’t done with osimertinib, and 2) it was a single institution in a country that’s not necessarily entirely reflective of our own healthcare situation here. The good thing is there is a big pharmaceutical study. FLAURA 2 is osimertinib plus or minus chemotherapy, which is going to answer that question.

Benjamin Levy, MD: I look forward to having that. I think the trial design is important to have to answer the question, does chemotherapy add anything to osimertinib versus osimertinib alone?

Zofia Piotrowska, MD: And it builds upon NEJ009. We did have another similar study out of Japan, which showed essentially very similar findings. I think this is a theme that we’re seeing over and over again. I think it will be really important to see this data with osimertinib because there is increased toxicity, practical considerations that we can’t discard. But I think for a really good improvement, people will adopt this.

Benjamin Levy, MD: Yes.

D. Ross Camidge, MD: And we should be clear, this is adding in chemotherapy, not chemoimmunotherapy.

Zofia Piotrowska, MD: Yes.

D. Ross Camidge, MD: That may be, if we’re drifting away from chemoimmunotherapy in EGFR-mutated, this may be a blessing in disguise as a way of getting that message home.

Transcript Edited for Clarity
 

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Transcript:

Benjamin Levy, MD: Let’s move on to some of the data we saw at ASCO [the American Society of Clinical Oncology annual meeting] today in the oral sessions. We’re trying to move the bar forward and looking at optimizing treatment for patients with EGFR-mutated lung cancer. This speaks to the heterogeneity of EGFR-mutated lung cancer. We’re starting to see signals of adding chemotherapy or antiangiogenesis drugs up front that may lead to improved outcomes. Ross, do you want to tackle abstract number 9001, which was essentially looking at gefitinib versus gefitinib plus chemotherapy, some of the data we saw last year at ASCO, in another dataset now?

D. Ross Camidge, MD: It was wonderful on several levels. One, it was the first really good data I’ve seen coming out of an Indian institution—tremendously enthusiastic and very impressive presenter. This was a home-grown study. EGFR-mutated patients, several hundred patients randomized to getting gefitinib or gefitinib plus carboplatin and pemetrexed. And it was quite dramatic. It increased the response rate. It doubled the PFS [progression-free survival] from something like 8 to 16 months, so it’s easy to figure out the hazard ratio, it’s 0.5. And it even increased overall survival [OS].

Now, with overall survival, the issue is in that setting, the ability to get next line therapy may be problematic. For example, in the control arm only 30% of people got chemotherapy. There’s an element  that you’re just stacking the deck up front. But it really makes you pause for thought. Is this something that is the best thing for our patients, recognizing that there’s an element of back to the future with this? It’s like we’re going back to chemotherapy after we said, great, you just get a pill? It really makes you think about whether you could have that discussion with a patient and say, look, there’s this data out there. OK, it was a single site, it was a big study, it was randomized, but what do you think about adding in some chemotherapy up front?

Benjamin Levy, MD: Are you ready to extrapolate and add it to osimertinib? I mean, we’ve got 2 datasets now showing that chemotherapy added to first-generation TKI [tyrosine kinase inhibitor] leads to these whopping improvements in OS that we don’t normally see. Is that a consideration right now? I know it’s not approved, but is there a patient where you may think, look, I’ve got this data with first-generation TKI showing a survival advantage, symptomatic patient, think you can tolerate, very young, would you add chemotherapy ever?

D. Ross Camidge, MD: The great thing is, so the 2 concerns are 1) it wasn’t done with osimertinib, and 2) it was a single institution in a country that’s not necessarily entirely reflective of our own healthcare situation here. The good thing is there is a big pharmaceutical study. FLAURA 2 is osimertinib plus or minus chemotherapy, which is going to answer that question.

Benjamin Levy, MD: I look forward to having that. I think the trial design is important to have to answer the question, does chemotherapy add anything to osimertinib versus osimertinib alone?

Zofia Piotrowska, MD: And it builds upon NEJ009. We did have another similar study out of Japan, which showed essentially very similar findings. I think this is a theme that we’re seeing over and over again. I think it will be really important to see this data with osimertinib because there is increased toxicity, practical considerations that we can’t discard. But I think for a really good improvement, people will adopt this.

Benjamin Levy, MD: Yes.

D. Ross Camidge, MD: And we should be clear, this is adding in chemotherapy, not chemoimmunotherapy.

Zofia Piotrowska, MD: Yes.

D. Ross Camidge, MD: That may be, if we’re drifting away from chemoimmunotherapy in EGFR-mutated, this may be a blessing in disguise as a way of getting that message home.

Transcript Edited for Clarity
 
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