ONCAlert | Upfront Therapy for mRCC

Case 2: Osimertinib in EGFR-Mutated Lung Cancer

Targeted Oncology
Published Online:1:11 PM, Thu June 20, 2019


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD: Just a reminder, you know we’ve had another practice-changing trial in the past 12 months, 24 months, published in the New England Journal of Medicine: the FLAURA data. This solidified a new standard of care for EGFR-mutant lung cancer. It was a very clean study. Patients who were stage IV exon 19 or exon 21 mutated, randomized 1 to 1 to osimertinib versus first-generation TKI [tyrosine kinase inhibitor]. There was an improvement in progression-free survival. There was an improvement in CNS [central nervous system] progression-free survival. This drug, osimertinib, does a wonderful job crossing the blood brain barrier, which I think is important for patients with brain metastases. For patients who are EGFR mutated who may have brain metastases, maybe we pump the brakes on radiation, give them this drug, and see what it can do in the brain.

Then we’re starting to see trends in overall survival. Keep in mind we’ve yet to see in very large phase III studies survival advantages between 2 TKIs and EGFR-mutant lung cancer. We’re starting to see this trend. The data are too early, but this may suggest that if this holds up, this would be 1 of the first trials where we’ve seen overall survival advantage. All patients seem to benefit from this trial. I’d make the argument that for osimertinib, what we thought was a T790M-directed therapy really is the de facto standard of care for EGFR mutant. I don’t know if you wrestle with any other TKIs in your practice as first-line therapy.

Isabel Preeshagul, DO, MBS: I have inherited some patients who are on first-generation TKIs, in which case I have had exposure to that. In other cases, I’ve had patients who have had progression on frontline carboplatin-pemetrexed-pembrolizumab and found that they actually had an EGFR mutation. So what would be the best TKI to offer them in that setting as well with the risk of pneumonitis?

Benjamin P. Levy, MD: Right. Do you have any toxicity concerns with osimertinib at all? Have you seen toxicity at all with this drug?

Isabel Preeshagul, DO, MBS: I actually have found it to be very well tolerated.

Benjamin P. Levy, MD: I have as well. Even though we’ve always thought of TKIs as rationed diarrhea, we just haven’t seen that with this drug, and it’s been a welcome change, obviously based on the data for doctors, but perhaps more for toxicity concerns for patients.

Samuel Caughron, MD: I wanted to go back to the discussion about EGFR and the timing of the testing. EGFR is done in virtually every next-generation sequencing panel, but it can also be done in many places as single hot spot testing. Precisely for the turnaround-time reason, it’s 1 of the reasons we still do it first as a hot spot. If it’s a hot spot, we can get that out within 3 days.

Benjamin P. Levy, MD: Do you do a hot spot followed by that? You do your molecular testing sequentially, or is it done altogether and you send everything out at the same time?

Samuel Caughron, MD: We have it in-house, so we’ve been able to optimize a timeline. We do the core panel within 3 to 5 days in all patients reflexively. We have not yet moved to a primary next-generation sequencing. We brought that in-house, and we’re looking at it. I think we will be there soon. The problem is turnaround time. It’s select patients. Another option potentially to the liquid biopsy is to ask for the hot-spot EGFR, especially in a patient like this who’s a nonsmoker.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD: Just a reminder, you know we’ve had another practice-changing trial in the past 12 months, 24 months, published in the New England Journal of Medicine: the FLAURA data. This solidified a new standard of care for EGFR-mutant lung cancer. It was a very clean study. Patients who were stage IV exon 19 or exon 21 mutated, randomized 1 to 1 to osimertinib versus first-generation TKI [tyrosine kinase inhibitor]. There was an improvement in progression-free survival. There was an improvement in CNS [central nervous system] progression-free survival. This drug, osimertinib, does a wonderful job crossing the blood brain barrier, which I think is important for patients with brain metastases. For patients who are EGFR mutated who may have brain metastases, maybe we pump the brakes on radiation, give them this drug, and see what it can do in the brain.

Then we’re starting to see trends in overall survival. Keep in mind we’ve yet to see in very large phase III studies survival advantages between 2 TKIs and EGFR-mutant lung cancer. We’re starting to see this trend. The data are too early, but this may suggest that if this holds up, this would be 1 of the first trials where we’ve seen overall survival advantage. All patients seem to benefit from this trial. I’d make the argument that for osimertinib, what we thought was a T790M-directed therapy really is the de facto standard of care for EGFR mutant. I don’t know if you wrestle with any other TKIs in your practice as first-line therapy.

Isabel Preeshagul, DO, MBS: I have inherited some patients who are on first-generation TKIs, in which case I have had exposure to that. In other cases, I’ve had patients who have had progression on frontline carboplatin-pemetrexed-pembrolizumab and found that they actually had an EGFR mutation. So what would be the best TKI to offer them in that setting as well with the risk of pneumonitis?

Benjamin P. Levy, MD: Right. Do you have any toxicity concerns with osimertinib at all? Have you seen toxicity at all with this drug?

Isabel Preeshagul, DO, MBS: I actually have found it to be very well tolerated.

Benjamin P. Levy, MD: I have as well. Even though we’ve always thought of TKIs as rationed diarrhea, we just haven’t seen that with this drug, and it’s been a welcome change, obviously based on the data for doctors, but perhaps more for toxicity concerns for patients.

Samuel Caughron, MD: I wanted to go back to the discussion about EGFR and the timing of the testing. EGFR is done in virtually every next-generation sequencing panel, but it can also be done in many places as single hot spot testing. Precisely for the turnaround-time reason, it’s 1 of the reasons we still do it first as a hot spot. If it’s a hot spot, we can get that out within 3 days.

Benjamin P. Levy, MD: Do you do a hot spot followed by that? You do your molecular testing sequentially, or is it done altogether and you send everything out at the same time?

Samuel Caughron, MD: We have it in-house, so we’ve been able to optimize a timeline. We do the core panel within 3 to 5 days in all patients reflexively. We have not yet moved to a primary next-generation sequencing. We brought that in-house, and we’re looking at it. I think we will be there soon. The problem is turnaround time. It’s select patients. Another option potentially to the liquid biopsy is to ask for the hot-spot EGFR, especially in a patient like this who’s a nonsmoker.

Transcript edited for clarity.
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