Immune Checkpoint Inhibitors in NSCLC Therapy

Edward Arrowsmith, MD: The checkpoint inhibitors really are agents that have revolutionized treatment. For those of us who've been treating non-small cell lung cancer for years or decades, we're seeing durable responses that are unbelievable compared with what we saw 10 or 15 years ago with patients free of symptoms of disease for 3, 4, 5, or more years down the road. These are agents that we integrated quickly into the therapy of non-small cell lung cancer and into our pathways program. We utilize them both as single agents and combined with chemotherapy, as well as following chemotherapy radiation or adjuvant therapy. They're spreading across the landscape in lung cancer therapy.

As the checkpoint inhibitors have been combined with chemotherapy, we've been fortunate that we've seen very high-quality data with large differences in outcomes between the chemotherapy alone arms and the chemotherapy plus checkpoint inhibitor arms. What we've seen recently, however, is a proliferation of different strategies, whether it's limited cycles of chemotherapy followed by checkpoint inhibitors or combinations of PD-L1 and CTLA4-targeted drugs. The landscape has gotten more complex. As to our pathways program, we tend to point clinicians towards a chemoimmunotherapy backbone and, depending on the details of adverse events, push clinicians towards specific combinations and away from others.

The chemotherapy checkpoint inhibitor landscape is complicated. There are some situations where there might be a clinical reason to use one checkpoint inhibitor [over] another. There are other circumstances where the trials appeared to be similar. A couple years ago, I was a co-author on a paper where we argued that, unlike 10 or 15 years ago where generic substitution of paclitaxel offered a lot of value compared with docetaxel or gemcitabine that were then name-branded products, there weren't a lot of roles for pathways driving values. Since that paper was published, we are returning to an era of clinical equipoise, where some of the checkpoint inhibitor studies look to me and to other experts, that the results are similar enough that choosing one checkpoint inhibitor to maximize value does make sense. Some of the economic considerations of cost for the patient and the health care system are going to come back into play. That's something we're actively looking at at OneOncology.

Transcript edited for clarity.