PD-1 Inhibition in Lung Cancer

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Immunotherapy continues to advance as a treatment for patients with non-small cell lung cancer (NSCLC), placing the focus on treatment selection, toxicity management, and the optimal sequencing of agents, states Corey J. Langer, MD. Clinical trials have shown promising efficacy for the PD-1 and the PD-L1 inhibitors in patients with refractory NSCLC, with response rates near 20%.

The immune checkpoint inhibitors will shift the treatment paradigm for patients with lung cancer, specifically since these agents appear effective in squamous and non-squamous disease, Roy S. Herbst, MD, PhD, explains. Distinct populations of patients appear to benefit the most from these therapies, with survival curves showing a distinct plateau. To find these long-term responders, work is being done to identify a biomarker of response.

A number of phase III studies are currently underway, which will provide more information. Additionally, the checkpoint inhibitors are now being moved into the first-line setting for patients with advanced NSCLC, notes Herbst. A phase I study presented at the ASCO Annual Meeting demonstrated a response rate of 30% in chemotherapy-naive patients with NSCLC treated with nivolumab. In PD-L1-positive patients, the response rate was 50%. The immune system might be stronger in the frontline setting, eliciting a better response, postulates Herbst.

Patients with PD-L1-negative disease still experience a response to PD-1 inhibitors, notes Ramaswamy Govindan, MD. As a result, it is unclear which patients should receive treatment. At this point, those with PD-L1-negative NSCLC should not be omitted from receiving the checkpoint inhibitors, Govindan believes.

Tumors with a high mutation burden respond very well to immune checkpoint inhibitors, Govindan notes. Additionally, other biomarkers are being explored, including PD-L1. Research is currently looking at the predictive value of regulatory T cells and RNA profiles for treatment selection, specifically as these agents move into the frontline setting, Herbst notes.