Matthew D. Hellmann, MD, assistant attending physician, Memorial Sloan Kettering Cancer Center, discusses the process of tumor mutational burden (TMB) testing in patients with lung cancer.

Physicians have increasingly started to visualize lung cancer as a pie chart in which patients are defined by their distinct biology. 

 are all examples of identified molecular markers that specific therapies can target.

Although TMB might sound as if it's a separate test, Hellman says it is actually additional data physicians get from the routine molecular analysis, which should be done in all patients with lung cancer. Molecular profiling has enabled physicians to understand both molecular aberrations and TMB. This ultimately brings a new piece of the pie that contains specific therapy indications with exceptional opportunity for long-term benefit, says Hellman.

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Dr. Hellmann on Tumor Mutational Burden Testing in Patients With Lung Cancer

Matthew D. Hellmann, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the role tumor mutational burden (TMB) plays in determining combination therapies for patients with non—small cell lung cancer (NSCLC).

At first, people were uncertain whether or not TMD was truly identifying predictive markers. Emerging data has clarified that it is a predictive marker. Randomized studies of patients treated with PD-1 monotherapy or chemotherapy showed that only those patients who received PD-1 therapy had improvement based on TMD.

When researchers first looked at TMD as a biomarker they focused on patients treated with PD-1 monotherapy. There was uncertainty about whether or not the same sort of correlation would be seen in patients who received combination immunotherapy. Investigators wondered whether the additional immunotherapy might broaden the immune response that occurred and consequently diminish the importance of TMD.

However, the opposite is true in patients with both NSCLC and small cell lung cancer. TMD may matter even more in patients treated with combination immunotherapy. It has been a successful biomarker, particularly in patients treated with combination immunotherapy.

Matthew D. Hellmann, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the role tumor mutational burden (TMB) plays in determining combination therapies for patients with non–small cell lung cancer (NSCLC).

Dr. Hellmann on Tumor Mutational Burden in NSCLC

Matthew D. Hellmann, MD, Memorial Sloan Kettering Cancer Center, discusses the design of the CheckMate-032 study investigating nivolumab (Opdivo) with or without ipilimumab (Yervoy) for patients with small cell lung cancer (SCLC).

There were 150 patients were assigned to receive either nivolumab or nivolumab plus ipilimumab in the nonrandomized cohort of the study, explains Hellmann.

The response rates of nivolumab plus ipilimumab was 23% compared with 11% with patients who receive nivolumab, states Hellmann.

Dr. Hellmann on the Design of the CheckMate-032 Study for Lung Cancer

Matthew D. Hellmann, MD, Memorial Sloan Kettering Cancer Center, discusses the CheckMate-032 study investigating nivolumab (Opdivo) with or without ipilimumab (Yervoy) for patients with small cell lung cancer (SCLC).

CheckMate-032 is a phase I/II study investigating patients with SCLC who were treated with or without ipilimumab, explains Hellmann. This study was conducted because outcomes and treatment options for patients with SCLC are poor.

A total of 150 patients with SCLC were designed to receive ipilimumab or nivolumab, states Hellmann. Since there were early signs of promising efficacy, nivolumab with or without ipilimumab was added to the NCCN guidelines.

This also prompted a randomized study where 250 patients were randomized to either nivolumab alone or nivolumab with ipilimumab, in order to confirm efficacy and determine potential biomarkers.

Matthew D. Hellmann, MD

Articles

Dr. Hellmann on Tumor Mutational Burden Testing in Patients With Lung Cancer

Dr. Hellmann on Tumor Mutational Burden in NSCLC

Dr. Hellmann on the Design of the CheckMate-032 Study for Lung Cancer

Dr. Hellmann on Nivolumab in Combination with Ipilimumab for Small Cell Lung Cancer