Jamie E. Chaft, MD

Jamie E. Chaft, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, discusses predictive biomarkers in lung cancer.

Rare mutations detected through next-generation sequencing have shown correlation to response in patients with advanced disease, says Chaft; however, tumor mutational burden (TMB) is a non–PD-L1 biomarker ​that appears to have utility in the lung cancer space​.

Although this biomarker has been subject to debate, TMB has a role in this space, according to Chaft. Research efforts should focus on centrally validating a way to test and define TMB, explains Chaft. 

Additionally, it is unknown whether patients who do not have high PD-L1 expression but have a high TMB will respond to immunotherapy, adds Chaft. Although it is likely that these patients will respond to this approach, prospective studies with monotherapies must be done in that patient population, especially given the toxicity concerns associated with ipilimumab (Yervoy) and nivolumab (Opdivo), says Chaft.

Although TMB appears to be the best biomarker thus far for immunotherapy, ​additional biomarkers are needed, as none of them are on par with established oncogene predictive markers, concludes Chaft. 

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Jamie E. Chaft, MD, discusses predictive biomarkers in lung cancer.

Dr. Chaft on Predictive Biomarkers in Lung Cancer

Jamie E. Chaft, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, discusses considerations for restarting immunotherapy in patients with lung cancer.

It was once believed that all immune-related adverse events (IRAEs) were solely T-cell mediated. Now, it’s widely understood that not all IRAEs are created equal, says Chaft; some of these events may be T-cell mediated while others, such as thyroiditis, may be B-cell mediated. Others can experience cytokine-mediated events.

Since IRAEs are not created equal, they should be managed on an individualized basis, adds Chaft. Each event has a different level of severity and duration of impact on patients. IRAEs require a different level of consideration when determining whether to restart immunotherapy in a patient, explains Chaft. 

These events need to be thoroughly evaluated and intervened upon to prevent harm to the patient. One of the most common interventions is either topical or systemic corticosteroids. Sometimes steroid-sparing agents are used to prevent steroid-induced AEs, such as osteoporosis and gastritis, concludes Chaft. 

Jamie E. Chaft, MD, discusses considerations for restarting immunotherapy in patients with lung cancer.

Dr. Chaft on Considerations for Restarting Immunotherapy in Lung Cancer

Jamie E. Chaft, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, discusses considerations for restarting immunotherapy in patients with lung cancer.

It was once believed that all immune-related adverse events (IRAEs) were solely T-cell mediated. Now, it’s widely understood that not all IRAEs are created equal, says Chaft; some of these events may be T-cell mediated while others, such as thyroiditis, may be B-cell mediated. Others can experience cytokine-mediated events.

Since IRAEs are not created equal, they should be managed on an individualized basis, adds Chaft. Each event has a different level of severity and duration of impact on patients. IRAEs require a different level of consideration when determining whether to restart immunotherapy in a patient, explains Chaft.

These events need to be thoroughly evaluated and intervened upon to prevent harm to the patient. One of the most common interventions is either topical or systemic corticosteroids. Sometimes, steroid-sparing agents are used to prevent steroid-induced AEs, such as osteoporosis and gastritis, concludes Chaft. 

Jamie E. Chaft, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the emergence of immunotherapy in stage IV lung cancer.

The introduction of immunotherapy to the lung cancer armamentarium was initially met with some skepticism, says Chaft. However, immunotherapy has found its role in the frontline setting.

Studies have demonstrated that the combination of chemotherapy and immunotherapy is superior to chemotherapy alone in selected patient populations with small cell lung cancer and non&shy;—small cell lung cancer, (NSCLC), explains Chaft. However, the magnitude of benefit for the general lung cancer population is not as significant.

Although most patients with stage IV disease will receive frontline immunotherapy, it may not be the optimal treatment for patients with actionable oncogenic drivers.

The utility of single-agent immunotherapy versus chemoimmunotherapy, as well as optimal sequencing strategies remain are under active investigation, as is the field of biomarker development, concludes Chaft.

Jamie E. Chaft, MD, discusses the emergence of immunotherapy in stage IV lung cancer.



Author | Jamie E. Chaft, MD

Articles

Dr. Chaft on Predictive Biomarkers in Lung Cancer

Dr. Chaft on Considerations for Restarting Immunotherapy in Lung Cancer

Dr. Chaft on Considerations for Restarting Immunotherapy in Lung Cancer

Dr. Chaft on the Emergence of Immunotherapy in Stage IV Lung Cancer