Complexities of Translating PD-1/PD-L1 Agents to Clinical Practice Emerge

By Sara L. Thier, PhD, MPH
Published: Tuesday, Jan 20, 2015

Antibody-Based Cancer Immunotherapy


MODERATOR

Louis M. Weiner, MD
Director, Georgetown Lombardi Comprehensive Cancer Center Chairman, Department of Oncology Francis L. and Charlotte G. Gragnani Chair Georgetown University Medical Center Washington, DC


PANELISTS

Robert Dreicer, MD, MS
Division of Hematology and Oncology Department of Medicine University of Virginia School of Medicine Charlottesville, VA

Omid Hamid, MD
Chief, Translational Research Immunotherapy Director, Melanoma Program The Angeles Clinic and Research Institute Santa Monica, CA

Roy S. Herbst, MD, PhD
Ensign Professor of Medicine (Medical Oncology) Chief, Medical Oncology Associate Director, Translational Research Yale Cancer Center Yale School of Medicine New Haven, CT

Mark A. Socinski, MD
Professor, Medicine and Thoracic Surgery Director, Lung Cancer Section UPMC Lung Cancer Center of Excellence Pittsburg, PA
As varying immunotherapy options become available for different types of cancers, researchers will have to take the next steps in clinical studies and in practice before the growing excitement over emerging agents can truly be translated into beneficial new therapies for patients, according to experts who participated in a recent OncLive Peer Exchange program.

Leading researchers discussed a broad range of considerations that have become evident in the development of immunomodulatory therapies during a recent Peer Exchange session entitled “Antibody- Based Cancer Immunotherapy,” that focused, in particular, on agents that target programmed cell death-1 (PD-1) and its ligand, PD-L1.

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Louis M. Weiner, MD

Louis M. Weiner, MD, who served as moderator of the discussion, said he believes that immunotherapy will work on every tumor type, but that complex scientific questions about which patients will benefit must be investigated. He stressed that in the future, researchers and clinicians will have to recognize that the heterogeneity of cancers, “… is going to become a critical determinant of who responds, how well they respond, and if they do relapse, how they relapse. And the challenge before us as clinical investigators and before our scientific colleagues is going to be to dive down deeply and understand what some of those mechanisms are and how the selection pressures influence these processes. And I think that preclinical models can help us with this, but…we’re also going to have to figure out how to do clinical trials that allow us to interrogate some of these concepts in a prospective way as well. So it’s very challenging but really quite exciting, I think.”

Although activating the immune system as a therapeutic approach in cancer has long been a cooperative goal between immunology and oncology, the FDA’s approval of the anti-CTLA4 antibody ipilimumab for melanoma in 2011 acted as a springboard for the current research focus. Immune checkpoint blockade therapy engages antibodies targeting T-cell inhibitory pathways, such as CTLA-4 and PD-1/ PD-L1, and is emerging as an important strategy in cancer immunotherapy.

Demonstrated efficacy and safety of the antibody- mediated PD-1 blockade strategy in the setting of melanoma led to the FDA approval of pembrolizumab in September 2014 and nivolumab in December 2014 for the treatment of metastatic melanoma. These and other PD-1/PD-L1-targeted agents, as well as additional immune checkpoint modulators, are under investigation as treatment in both solid tumor and hematologic cancers.1

Continued Progress in Melanoma

With the approval of these two additional immune checkpoint agents, the treatment of melanoma continues to advance. Researchers are now looking at the most effective use of these agents as either monotherapy and in combination with other immunotherapy agents and targeted therapies.

Omid Hamid, MD

Tolerability and the development of predictive biomarkers that guide treatment selection will determine the future role of checkpoint inhibitors in melanoma, said Omid Hamid, MD.


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