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Small-Cell Lung Cancer: Future Directions in Care

Insights From: Stephen Liu, MD, Georgetown University; Benjamin P. Levy, MD, John Hopkins Sidney Kimmel Cancer Center
Published: Friday, Apr 03, 2020



Transcript: 

Benjamin P. Levy, MD:
There are a lot of challenges that we have with small-cell lung cancer. Small-cell lung cancer, unlike non–small-cell lung cancer, hasn’t shared in the same advances. We can’t parse out small-cell lung cancer into molecular subsets, unfortunately, like we can with non–small-cell lung cancer. We can’t deliver targeted therapies the way we do for non–small-cell lung cancer. The strategies that we implement have to be innovative, and we have to learn more about tumor biology with small-cell lung cancer. We do know that it’s addicted to transcription. We know that there may be strategies for epigenetic modulation. We know there are strategies to exploit metabolic pathways in small-cell lung cancer.

There are a lot of different ways to look at this. It can’t be looked at in the same way as the prism of non–small-cell lung cancer. We have to think a little differently about the tumor biology. I think we’ve made some advances with immunotherapy and with novel chemotherapies like lurbinectedin, but we have a long way to go. And we are pushing the envelope with a better understanding of transcriptional activation in small-cell lung cancer and the different molecular subsets based on differential transcriptional activation. We’re still very early on in this story. I look forward to improving the outcomes or being part of the story of delivering some of these drugs for small-cell lung cancer.

Stephen Liu, MD: There are some reasons to be excited when we look at the outlook for small-cell lung cancer over the next few years. We’ve now had 2 studies that have shown the addition of a PD-L1 [programmed death-ligand 1] inhibitor to standard platinum doublet chemotherapy has improved survival. This is the first intervention that’s had any impact on survival for small-cell lung cancer in several decades. Where do we go from here? How do we increase that potential impact? It really comes down to biomarkers and dividing certain populations apart.

We know that small-cell lung cancer is not 1 disease, that there’s a lot of heterogeneity, and that the benefit from immunotherapy is likely carried by a small subset of patients. It is now our job to identify who those patients are so we can make sure those patients receive that therapy and, for patients who are destined to get that long-term benefit from immunotherapy with chemotherapy, to develop newer strategies.

Multiple randomized trials are being launched now looking at different immunotherapy targets, different checkpoint inhibitors, and the incorporation of PARP inhibitors. Doing so in an empiric manner will be a great challenge, and identifying specific subsets within small-cell lung cancer really is the key to making the large strides that we’ve seen in non–small-cell lung cancer. We’re excited by new standards of care. We have new, exciting molecules being launched in trials now. The next big step will really require the development of reliable and useful biomarkers for this disease.


Transcript Edited for Clarity
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Transcript: 

Benjamin P. Levy, MD:
There are a lot of challenges that we have with small-cell lung cancer. Small-cell lung cancer, unlike non–small-cell lung cancer, hasn’t shared in the same advances. We can’t parse out small-cell lung cancer into molecular subsets, unfortunately, like we can with non–small-cell lung cancer. We can’t deliver targeted therapies the way we do for non–small-cell lung cancer. The strategies that we implement have to be innovative, and we have to learn more about tumor biology with small-cell lung cancer. We do know that it’s addicted to transcription. We know that there may be strategies for epigenetic modulation. We know there are strategies to exploit metabolic pathways in small-cell lung cancer.

There are a lot of different ways to look at this. It can’t be looked at in the same way as the prism of non–small-cell lung cancer. We have to think a little differently about the tumor biology. I think we’ve made some advances with immunotherapy and with novel chemotherapies like lurbinectedin, but we have a long way to go. And we are pushing the envelope with a better understanding of transcriptional activation in small-cell lung cancer and the different molecular subsets based on differential transcriptional activation. We’re still very early on in this story. I look forward to improving the outcomes or being part of the story of delivering some of these drugs for small-cell lung cancer.

Stephen Liu, MD: There are some reasons to be excited when we look at the outlook for small-cell lung cancer over the next few years. We’ve now had 2 studies that have shown the addition of a PD-L1 [programmed death-ligand 1] inhibitor to standard platinum doublet chemotherapy has improved survival. This is the first intervention that’s had any impact on survival for small-cell lung cancer in several decades. Where do we go from here? How do we increase that potential impact? It really comes down to biomarkers and dividing certain populations apart.

We know that small-cell lung cancer is not 1 disease, that there’s a lot of heterogeneity, and that the benefit from immunotherapy is likely carried by a small subset of patients. It is now our job to identify who those patients are so we can make sure those patients receive that therapy and, for patients who are destined to get that long-term benefit from immunotherapy with chemotherapy, to develop newer strategies.

Multiple randomized trials are being launched now looking at different immunotherapy targets, different checkpoint inhibitors, and the incorporation of PARP inhibitors. Doing so in an empiric manner will be a great challenge, and identifying specific subsets within small-cell lung cancer really is the key to making the large strides that we’ve seen in non–small-cell lung cancer. We’re excited by new standards of care. We have new, exciting molecules being launched in trials now. The next big step will really require the development of reliable and useful biomarkers for this disease.


Transcript Edited for Clarity
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