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Targeting the Immune System in Non-Small Cell Lung Cancer

Panelists: Corey J. Langer, MD, Penn Medicine; Roy S. Herbst, MD, PhD, Yale;Karen L. Reckamp, MD, MS, City of Hope; Anne S. Tsao, MD, MD Anderson
Published: Wednesday, Oct 16, 2013
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Harnessing the immune system to treat patients with non-small cell lung cancer (NSCLC) represents a novel and exciting new treatment approach, explains Karen L. Reckamp, MD, MS. The most promising agents target the immune checkpoint PD-1 and its ligand, PD-L1. These agents work by inhibiting the tumor's defense mechanism that allows it to suppress antitumor immune activity. 

Agents that target immune checkpoints represent a possible shift in the treatment paradigm for patients with NSCLC, believes Roy S. Herbst, MD, PhD. The anti-PD-1 antibody nivolumab demonstrated response rates of up to 20% in patients with NSCLC, explains Herbst. Interestingly, many of these responses come in patients with difficult-to-treat tumors, such as RAS mutated and those refractory to EGFR or ALK targeted therapies. As a result, treatments in this class may be effective in both the refractory and frontline setting.

The median duration of response to PD-1-targeted agents lasts for a substantial period of time, notes Herbst. Furthermore, the response continues following the discontinuation of treatment, suggesting a reprogramming of the immune system to recognize the tumor.

Researchers are exploring possible markers of response for treatment with PD-1 inhibitors, such as PD-L1 expression. However, this investigation is particularly difficult, since PD-L1 expression can be induced by interferon-gamma, Herbst believes. As a result, the effectiveness of this marker is heavily reliant on the quality of the biopsy and tissue collected.

However, research into the PD-L1 inhibitor MPDL3280A seems to indicate that PD-L1 expression correlates to a better response in patients with NSCLC. A phase I study of 85 patients with NSCLC found a response rate of 21% that was enhanced to 46% for patients with PD-L1 expression. In addition to PD-L1, the investigation of other markers will continue to increase as the focus of research shifts toward combination strategies, believes Herbst.
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For High-Definition, Click
Harnessing the immune system to treat patients with non-small cell lung cancer (NSCLC) represents a novel and exciting new treatment approach, explains Karen L. Reckamp, MD, MS. The most promising agents target the immune checkpoint PD-1 and its ligand, PD-L1. These agents work by inhibiting the tumor's defense mechanism that allows it to suppress antitumor immune activity. 

Agents that target immune checkpoints represent a possible shift in the treatment paradigm for patients with NSCLC, believes Roy S. Herbst, MD, PhD. The anti-PD-1 antibody nivolumab demonstrated response rates of up to 20% in patients with NSCLC, explains Herbst. Interestingly, many of these responses come in patients with difficult-to-treat tumors, such as RAS mutated and those refractory to EGFR or ALK targeted therapies. As a result, treatments in this class may be effective in both the refractory and frontline setting.

The median duration of response to PD-1-targeted agents lasts for a substantial period of time, notes Herbst. Furthermore, the response continues following the discontinuation of treatment, suggesting a reprogramming of the immune system to recognize the tumor.

Researchers are exploring possible markers of response for treatment with PD-1 inhibitors, such as PD-L1 expression. However, this investigation is particularly difficult, since PD-L1 expression can be induced by interferon-gamma, Herbst believes. As a result, the effectiveness of this marker is heavily reliant on the quality of the biopsy and tissue collected.

However, research into the PD-L1 inhibitor MPDL3280A seems to indicate that PD-L1 expression correlates to a better response in patients with NSCLC. A phase I study of 85 patients with NSCLC found a response rate of 21% that was enhanced to 46% for patients with PD-L1 expression. In addition to PD-L1, the investigation of other markers will continue to increase as the focus of research shifts toward combination strategies, believes Herbst.
View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 18th Annual International Lung Cancer Congress®Oct 31, 20181.5
Clinical Interchange™: Translating Research to Inform Changing Paradigms: Assessment of Emerging Immuno-Oncology Strategies and Combinations across Lung, Head and Neck, and Bladder CancersOct 31, 20182.0
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