Joshua K. Sabari, MD

Joshua K. Sabari, MD, assistant professor, Department of Medicine, NYU Langone’s Perlmutter Cancer Center, discusses the management of immune-related adverse events (irAEs) in patients with lung cancer.

Immunotherapy drugs are safe and well-studied, says Sabari. As such, these drugs have an established set of irAEs. However, someone who is less familiar with these agents should always seek out a doctor or team that is more familiar with them. If certain questions or concerns arise about a rash or diarrhea, reach out to colleagues for help, advises Sabari. There are very common irAEs associated with this approach, which include thyroiditis, dermatitis, and colitis, and if these are identified early, patients can be safely treated, he says.

Other irAEs, such as pneumonitis, need to be taken more seriously. Patients who present with pneumonitis are often taken off the drug definitively. Working with rheumatology and endocrinology colleagues, as well as dermatologists, is critical in building that infrastructure so there is a good referral system in place for patients who experience these events, he concludes.

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Dr. Sabari on Managing Immune-Related Adverse Events in Lung Cancer

Joshua K. Sabari, MD, assistant professor, Department of Medicine, NYU Langone’s Perlmutter Cancer Center, discusses the utility of liquid biopsies in lung cancer.

Liquid biopsies are critical in patients who have a high likelihood of having a genetic driver alteration, says Sabari. Specifically, younger patients, and patients who are never-smokers; these are patients who should undergo standard immunohistochemistry for 

. In that setting, liquid biopsies are extremely helpful in identifying other alterations such as 

. They can also be used to identify other markers, such as 

 exon 14 skipping alterations, as well as 

 alterations—both mutations and amplifications, adds Sabari.

However, the cost of these tests is still an issue, as well as the setting in which they are ordered. For example, a physician may want to order a liquid biopsy to monitor disease response or residual disease, but there are no indications for that and no prospective studies showing their benefit. It is, however, indicated upfront, or when an alteration is identified in the face of a potential secondary resistance mechanism, explains Sabari.

 exon 19 activating deletion is started on osimertinib (Tagrisso) and the patient progresses 1 or 2 years later, using a liquid biopsy to identify alterations such as 

Dr. Sabari Discusses the Utility of Liquid Biopsies in Lung Cancer

Joshua K. Sabari, MD, assistant professor of medicine, NYU Langone's Perlmutter Cancer Center, discusses the role of immunotherapy in the treatment of patients with small cell lung cancer (SCLC).

SCLC is a difficult disease, Sabari says. Frontline chemotherapy seems to work very well, with response rates in the order of 70% to 80%. Unfortunately, all patients will eventually relapse with chemotherapy-refractory disease. Until the past year, no changes had been made beyond that setting in over 2 decades.

The first drug approval in over 20 years came in August 2018, when single-agent nivolumab (Opdivo) was granted an accelerated FDA approval for the treatment of patients with SCLC with disease progression following platinum-based chemotherapy and 1 other line of therapy. Objective response rates were low, at approximately 10%, Sabari notes, but the checkpoint inhibitor was still approved.

Additionally, atezolizumab (Tecentriq) in combination with platinum-based therapy and etoposide could also become the standard of care in the frontline setting, based on data from the IMpower133 study. Results of this trial demonstrated an estimated 2.0-month improvement in overall survival for the atezolizumab arm. Although this is modest, it is a major advance for the field, Sabari explains. Additional immunotherapy combinations could be a part of future SCLC management.

Joshua K. Sabari, MD, assistant professor of medicine, NYU Langone's Perlmutter Cancer Center, discusses the role of immunotherapy in the treatment of patients with small cell lung cancer.

Dr. Sabari Discusses Role of Immunotherapy in SCLC

Joshua K. Sabari, MD, assistant professor of medicine, NYU Langone's Perlmutter Cancer Center, discusses biomarkers of immunotherapy response in patients with non—small cell lung cancer (NSCLC).

The reliability of PD-L1 expression as a biomarker is up for debate in the field, but Sabari says he still orders PD-L1 testing for his patients and uses the 50% cutoff to define if a patient should receive pembrolizumab (Keytruda) alone or in combination with chemotherapy. He adds that he does this for patients presenting with non—small cell adenocarcinoma as well as those with squamous NSCLC.

Sabari notes that if you parse the data, no matter how you look at it, patients with high levels of PD-L1 expression have a greater chance to benefit from immunotherapy. His treatment approach is to weigh the risks of each therapy with the benefits. For example, if a patient has a PD-L1 expression of 100%, who he knows has a high likelihood of responding to immunotherapy, then chemotherapy can be avoided.

Another key biomarker coming down the pike is tumor mutational burden (TMB), he adds. Although this is a controversial topic, there are studies looking at it prospectively as well as retrospectively. For example, the CheckMate-227 trial, which was recently published, showed an improvement in patients who had high TMB. The controversy, he explains, lies in the question of how to define “TMB-high” and if it is possible to establish a unified definition by looking at different assays.

Joshua K. Sabari, MD, assistant professor of medicine, NYU Langone's Perlmutter Cancer Center, discusses biomarkers of immunotherapy response in non–small cell lung cancer.

Author | Joshua K. Sabari, MD

Articles

Dr. Sabari on Managing Immune-Related Adverse Events in Lung Cancer

Dr. Sabari Discusses the Utility of Liquid Biopsies in Lung Cancer

Dr. Sabari Discusses Role of Immunotherapy in SCLC

Dr. Sabari Discusses Immunotherapy Biomarkers in NSCLC