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Emerging Agents and Future of Small Cell Lung Cancer

*April 2021*

Stephen V. Liu, MD: Small cell lung cancer has such a high rate of attrition. The biggest impact will always be in the first-line setting. We’ll see empiric strategies that try to build on the chemoimmunotherapy approach validated by the IMpower133 and CASPIAN trials. The addition of thoracic radiation, alternate maintenance strategies, or incorporation of more immunomodulatory agents, like anti-TIGIT [T-cell immunoreceptor with immunoglobulin and ITIM domain] antibodies, will help build on those outcomes we see in extensive-stage small cell lung cancer. We’ll start to work on selective delivery of agents. We need to identify the unique subsets that exist within small cell lung cancer that can be treated differently. Empiric therapy is only going to take us so far. We desperately need predictive biomarkers that can guide therapy. There is a lot of enthusiasm for expression of transcriptional regulators as a guide. We still, however, need clinical data to validate this approach. Ultimately, we will need prospective data to see if this is an effective strategy going forward.

There are many active agents and combinations in development. Liposomal irinotecan was granted fast-track designation by the US FDA. In part 1, we saw a response rate of over 40%, which is exciting, but we need to wait for results from part 2, where patients are randomized to nal-IRI [nanoliposomal irinotecan] or topotecan. We need to reserve judgments for these agents until we see randomized data because we’ve seen responses before. A good example is amrubicin. In phase 2 studies, amrubicin showed high response rates, some over 50%, 60%. But in a randomized trial, those response rates didn’t translate to a survival benefit over standard topotecan. A similar example is the combination of lurbinectedin plus irinotecan. There was a high response rate, 62%, and 69% in chemotherapy-sensitive disease, but it’s not clear this is going to lead to any improvement in survival. In addition, that combination was fairly toxic, with 29% grade 3 diarrhea, 62% grade 3 neutropenia.

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