PD-1 and PD-L1 inhibition offers the possibility for precision immuno-oncology through the application of biomarkers that predict the immune systems response. This principle has been demonstrated by two of the most recent FDA approvals for patients with lung cancer.
In the first decision, the PD-1 inhibitor pembrolizumab (Keytruda) was granted an accelerated approval for pretreated patients with non–small cell lung cancer (NSCLC) who tests positive for PD-L1. This treatment was approved along with a companion diagnostic for selecting patients. In the pivotal trial that led to the drug's approval, those with PD-L1-positive disease were substantially more likely to respond compared with the negative group.
In a separate FDA decision, the FDA took a different course of action. In this decision, the PD-1 inhibitor nivolumab (Opdivo) was approved for pretreated patients with nonsquamous NSCLC. Although this decision was not specifically for those with PD-L1-positive lung cancer, it was approved along with a "complementary" PD-L1 diagnostic, to help guide treatment decisions.
As this field evolves, there will be many questions that still need to be answered. As Roy S. Herbst, MD, PhD, explained in the article, PD-L1 is only a moderately effective biomarker for immune checkpoint inhibitors and represents a few step in personalizing these therapies. Researchers are now digging deeper into predictors of response, including the BIM protein.
Biomarkers of response are not new to lung cancer; in fact, some could argue that NSCLC is furthest along in the race toward personalized medicine. Moving these advances beyond the established EGFR, ALK, and ROS1 biomarkers will represent the next challenge facing research.
Adjustments to clinical trial designs have already been made to shift the focus from histology to genomics. Umbrella, basket, and other novel clinical trial designs are enrolling participants based on their genetic alterations not type of cancer, with the hopes of uncovering truly personalized medicine.
As this research unfolds, Precision Medicine in Oncology
will continue to cover the latest advances and provide updates on the current trends in utilizing these new therapies.
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