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Dr. Antonia on Investigational Immunotherapy Combinations in Stage III NSCLC

Scott J. Antonia, MD, PhD
Published: Thursday, Jun 20, 2019



Scott J. Antonia, MD, PhD, instructor, Duke University School of Medicine, member, Duke Cancer Institute, discusses investigational immunotherapy combinations in stage III non–small cell lung cancer (NSCLC).

There are several potential combinations to explore in this space. However, no other immunotherapeutic agent has the degree of single-agent activity that has been shown with anti–PD-1/PD-L1 agents, Antonia says. The only way to capitalize on this activity is to develop combination immunotherapy, half of which should be directed to the lymphoid compartment to increase the number of tumor-reactive T cells, and the other half should be a continued blockade of anti–PD-1 in the tumor microenvironment. A manifestation of a productive antitumor T-cell response within the tumor microenvironment is the secretion of gamma interferon on other inflammatory cytokines that are potent inducers of PD-L1, explains Antonia.

In addition to developing synergistic combinations, there has to be a better understanding of how to employ biomarkers to select for patients on clinical trials. In stage III NSCLC, there is a lot of interest in exploring the combination of ipilimumab (Yervoy) with radiation and chemotherapy. One such trial that is currently accruing patients is looking at the combination of an anti–CTLA-4 agent, chemotherapy, and radiation therapy followed by consolidative anti–PD-1 therapy (NCT03663166).
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Scott J. Antonia, MD, PhD, instructor, Duke University School of Medicine, member, Duke Cancer Institute, discusses investigational immunotherapy combinations in stage III non–small cell lung cancer (NSCLC).

There are several potential combinations to explore in this space. However, no other immunotherapeutic agent has the degree of single-agent activity that has been shown with anti–PD-1/PD-L1 agents, Antonia says. The only way to capitalize on this activity is to develop combination immunotherapy, half of which should be directed to the lymphoid compartment to increase the number of tumor-reactive T cells, and the other half should be a continued blockade of anti–PD-1 in the tumor microenvironment. A manifestation of a productive antitumor T-cell response within the tumor microenvironment is the secretion of gamma interferon on other inflammatory cytokines that are potent inducers of PD-L1, explains Antonia.

In addition to developing synergistic combinations, there has to be a better understanding of how to employ biomarkers to select for patients on clinical trials. In stage III NSCLC, there is a lot of interest in exploring the combination of ipilimumab (Yervoy) with radiation and chemotherapy. One such trial that is currently accruing patients is looking at the combination of an anti–CTLA-4 agent, chemotherapy, and radiation therapy followed by consolidative anti–PD-1 therapy (NCT03663166).

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