Aiming for Precision Medicine in NSCLC - Episode 1
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A number of PD-1/PD-L1 checkpoint inhibitors are in clinical trials, including nivolumab, pembrolizumab, MPDL3280A, and MEDI4736. These agents work by blocking the interacton between PD-1 and its ligand PD-L1. In general, tumor cells express PD-L1, which binds to PD-1, causing T cells not to attack the tumor, Roy S. Herbst, MD, PhD, explains. PD-1/PD-L1 inhibitors block this interaction, allowing for an immune response.
While both classes of therapy are effective, there are subtle differences between the PD-1 and PD-L1 inhibitors, notes Herbst. Blocking PD-1 interferes with the cellular communication between PD-1 and both PD-L1 and PD-L2 whereas PD-L1 inhibitors leave PD-L2 intact, keeping this signaling pathway open. The differences in efficacy and side effects between these two mechanisms of actions are still being explored.
Promising findings have been seen with PD-1 inhibitors in non-small cell lung cancer (NSCLC), Thomas E. Stinchcombe, MD, explains. In the phase II CheckMate-063 trial, single-agent nivolumab was examined in heavily pretreated patients with advanced squamous cell NSCLC. At an 11-month follow-up, the objective response rate with nivolumab was 15%. The estimated 1-year survival rate was 41% and the median OS was 8.2 months. Additionally, in mid-January, phase III findings from the CheckMate-017 study demonstrated that nivolumab extended overall survival compared with docetaxel in patients with pretreated squamous cell NSCLC.
Treatment with the PD-1 inhibitors results in a minority of patients receiving a tremendous response, notes Stinchcombe. Research is still needed to find a biomarker of response, in order to guarantee that only patients who will respond receive treatment.