Julie R. Brahmer, MD, from Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, discusses immunotherapy and how it can advance as a treatment option for patients with lung cancer.

A continued and deeper understanding of lung cancer is necessary to understand how the disease shields itself from the immune system. Brahmer adds there should be more research on developing therapies that will target the immune system in various ways, and how they can possibly be combined with standard therapies.

The most important step for advancing immunotherapy is personalizing the treatment, Brahmer says. Such steps are already in the works, she adds, by seeking biomarkers for anti-PD-1 and anti-PD-L1 agents.

However, the necessary technology is not advancing at the rate in which these treatments are, Brahmer says.

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Dr. Brahmer on Immunotherapy Development in Lung Cancer

Julie R. Brahmer, MD, from Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, discusses how physicians distinguish between a response to an immunotherapy and cancer growth.

The main way this is distinguished is by looking at how the patient is doing, Brahmer says. If a patient is otherwise clinically well and their disease is getting slightly worse, a physician should allow for that patient to remain on immunotherapy for another cycle. If a patient’s disease continues to progress even if he/she is feeling well, Brahmer says, a physician should not keep their patient on the drug. If a patients is doing poorly and his/her cancer is progressing, it is definitely time that immunotherapy be discontinued, Brahmer says.

Dr. Brahmer on Distinguishing Between Response and Growth

Julie R. Brahmer, MD, from Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, discusses the management of adverse events (AEs) from treatment with immunotherapies.

Currently, Brahmer says she is taking a multidisciplinary approach to manage AEs, as she is not as experienced as some melanoma and renal cell carcinoma doctors, who have been treating with immunotherapies for some time.

Brahmer says it is beneficial to have other physicians to go to if any questions arise, such as a dermatologist, pulmonologist, or hepatologist. Over time, lung cancer doctors will become more comfortable in this space.

Dr. Brahmer Discusses Managing Immunotherapy AEs

Julie R. Brahmer, MD, from Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, explains the role of the PD-1 pathway and the ligands PD-L1 and PD-L2 in the regulation of the immune system.

Brahmer says the program death 1 (PD-1) pathway is a checkpoint pathway that controls immune response in the body to prevent extreme inflammation or other problems during illness.

PD-1 is a receptor on a T cell while its ligand, PD-L1, is expressed on peripheral tissues or tumor cells, Brahmer says. PD-1 has another ligand, PD-L2, which is also thought to be present on antigen-presenting cells or tumor cells, though research is ongoing.

When the T cell binds to one of its ligands, it deactivates the T cell, Brahmer says, protecting the tumor from the body’s immune system. When that response is blocked, the T cell can remain active and kill the tumor.

Julie R. Brahmer, MD, from Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, explains the role of PD-1 and PD-L1.

Dr. Julie Brahmer Explains the Role of PD-1 and PD-L1

Julie R. Brahmer, MD, Associate Professor, Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, discusses the future of antibodies, including nivolumab, for the treatment of lung cancer at the 11th Annual International Congress on Targeted Therapies in Cancer.

As more and more monoclonal antibodies are being tested in the clinic, it is enocouraging to see consistent responses across tumor types, Brahmer says. Based on these consistent responses, the oncology community hopes to get these antibodies approved for the treatment of patients with lung cancer.

In addition to continued consistent results, there is hope for a better safety profile with these agents. When responses are seen, Brahmer says, they are often long lasting. Unlike chemotherapy, which typically elicits a response of a few months, the duration of responses seen with nivolumab is unheard of.

Julie R. Brahmer, MD, from Johns Hopkins University School of Medicine, Sidney Kimmel Comprehensive Cancer Center, discusses the future of antibodies, including nivolumab, for the treatment of lung cancer.

Dr. Brahmer on the Future of Antibodies for Lung Cancer

Julie R. Brahmer, MD, associate professor of oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, discusses a phase I clinical trial that investigated the experimental agent BMS-936558, a targeted immunotherapy agent that blocks the programmed death-1 (PD-1) receptor that is expressed by activated T cells, in multiple tumor types.

Brahmer explains this trial is the second to investigate this antibody in clinical trials for humans. On the trial, patients received BMS-936558 once every two weeks in an eight-week cycle for up to two years. The trial enrolled 296 patents with advanced melanoma, non-small cell lung cancer (NSCLC), colorectal cancer, renal cell carcinoma (RCC), and prostate cancer.

The dose escalation portion of the trial provided doses between 0.1 to 10.0 mg/kg but did not find a maximum tolerated dose because all dose sizes were well tolerated. BMS-936558 was generally well tolerated and all side effects of the agent were similar to other immunotherapies and included pneumonitis, hypophysitis, hepatitis, colitis, and thyroiditis.

Activity was noted prominently in patients with melanoma (28% of patients), RCC (27%), and NSCLC (18%). Brahmer notes that some patients demonstrated a prolonged response to the therapy that lasted not only for the two years they received the agent but also an additional year after the therapy was stopped.

Dr. Julie Brahmer, from the Sidney Kimmel Comprehensive Cancer Center, on the PD-1 Immunotherapy BMS-93655 Clinical Trial

Julie R. Brahmer, MD

Articles

Dr. Brahmer on Immunotherapy Development in Lung Cancer

Dr. Brahmer on Distinguishing Between Response and Growth

Dr. Brahmer Discusses Managing Immunotherapy AEs

Dr. Julie Brahmer Explains the Role of PD-1 and PD-L1

Dr. Brahmer on the Future of Antibodies for Lung Cancer

Dr. Brahmer on the PD-1 Immunotherapy BMS-936558