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Immuno- and Chemotherapy Approach to R/R NSCLC

Insights From: Lyudmila A. Bazhenova, MD, UC San Diego Health; Ross Camidge, MD, PhD, University of Colorado Cancer Center
Published: Tuesday, Feb 04, 2020



Transcript: 

Lyudmila A. Bazhenova, MD:
One very important point to cover when you make a decision how to treat patients with ALK-fused non–small cell lung cancer when newly diagnosed, is to point out that chemoimmunotherapy would not be an appropriate choice for those patients. None of our trials that looked at efficacy of carboplatinum, pemetrexed, pembrolizumab, in stage IV newly diagnosed non–small cell lung cancer, such as KEYNOTE-021G and KEYNOTE-189, were allowing patients with either EGFR or ALK inhibition.

So we truly have no evidence that addition of immunotherapy to chemotherapy, or immunotherapy by itself, such as KEYNOTE-024 or KEYNOTE-042, has efficacy in patients with ALK-mutated non–small cell lung cancer. I definitely would not recommend using monotherapy immunotherapy as a first-line treatment option in your patients with ALK-fused non–small cell lung cancer, neither will I recommend using chemotherapy plus immunotherapy in those populations, just because those patients were not included in the trials. The only immunotherapy trial that used combination of immunotherapy plus chemotherapy that allowed ALK-fused patients was a trial called IMpower150. In that trial, only patients who had been exposed and failed all the appropriate ALK tyrosine kinase inhibitors were enrolled. So for your patients who are newly diagnosed, who you’re making a decision for what to do, if you know that your patient has an ALK mutation, ALK tyrosine kinase inhibitors would be the most appropriate choice. We have looked at efficacy of monotherapy PD-1 [programmed cell death protein 1] inhibitors in patients with ALK-mutated non–small cell lung cancer, and the data so far are pretty inferior.

There are several studies looking at either a retrospective analysis or prospective analysis or subset analysis of efficacy of monotherapy PD-1 inhibitors in that patient population, and there are studies that showed that response rate is 0. There are some studies that showed that response rate is pretty low, in the single digits, like 9%, maybe 10%. So outside of the clinical trial, I personally do not use monotherapy PD-L1 [programmed death-ligand 1] inhibition in ALK-mutated non–small cell lung cancer, unless I exhausted all my other options, meaning all ALK tyrosine kinase inhibitors that have efficacy, platinum doublet, and maybe monotherapy chemotherapy, before I consider PD-1 or PD-L1 inhibition as a single agent in that patient population.

Transcript Edited for Clarity
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Transcript: 

Lyudmila A. Bazhenova, MD:
One very important point to cover when you make a decision how to treat patients with ALK-fused non–small cell lung cancer when newly diagnosed, is to point out that chemoimmunotherapy would not be an appropriate choice for those patients. None of our trials that looked at efficacy of carboplatinum, pemetrexed, pembrolizumab, in stage IV newly diagnosed non–small cell lung cancer, such as KEYNOTE-021G and KEYNOTE-189, were allowing patients with either EGFR or ALK inhibition.

So we truly have no evidence that addition of immunotherapy to chemotherapy, or immunotherapy by itself, such as KEYNOTE-024 or KEYNOTE-042, has efficacy in patients with ALK-mutated non–small cell lung cancer. I definitely would not recommend using monotherapy immunotherapy as a first-line treatment option in your patients with ALK-fused non–small cell lung cancer, neither will I recommend using chemotherapy plus immunotherapy in those populations, just because those patients were not included in the trials. The only immunotherapy trial that used combination of immunotherapy plus chemotherapy that allowed ALK-fused patients was a trial called IMpower150. In that trial, only patients who had been exposed and failed all the appropriate ALK tyrosine kinase inhibitors were enrolled. So for your patients who are newly diagnosed, who you’re making a decision for what to do, if you know that your patient has an ALK mutation, ALK tyrosine kinase inhibitors would be the most appropriate choice. We have looked at efficacy of monotherapy PD-1 [programmed cell death protein 1] inhibitors in patients with ALK-mutated non–small cell lung cancer, and the data so far are pretty inferior.

There are several studies looking at either a retrospective analysis or prospective analysis or subset analysis of efficacy of monotherapy PD-1 inhibitors in that patient population, and there are studies that showed that response rate is 0. There are some studies that showed that response rate is pretty low, in the single digits, like 9%, maybe 10%. So outside of the clinical trial, I personally do not use monotherapy PD-L1 [programmed death-ligand 1] inhibition in ALK-mutated non–small cell lung cancer, unless I exhausted all my other options, meaning all ALK tyrosine kinase inhibitors that have efficacy, platinum doublet, and maybe monotherapy chemotherapy, before I consider PD-1 or PD-L1 inhibition as a single agent in that patient population.

Transcript Edited for Clarity
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