Benjamin P. Levy, MD

Benjamin P. Levy, MD, an associate professor at Johns Hopkins School of Medicine and clinical director for the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses biomarkers that have led to the development therapies with high response rates in lung cancer.

, the first space to gain a lot of traction was

fusions, says Levy. Crizotinib (Xalkori) is available for&nbsp;

fusions, but more recent data has led to the use of ceritinib (Zykadia), and now entrectinib (Rozlytrek), lorlatinib (Lorbrena), and repotrectinib (TPX-0005).&nbsp;&nbsp;When used as single-agents, these 3 new therapies have demonstrated response rates around 70% to 80% and a median progression-free survival of 19 to 20 months.

More recently, Levy says these drugs have shown to have activity in patients who have already received crizotinib, such as lorlatinib and repotrectinib. Levy notes we are learning about

, which is that we are learning to sequence these drugs to optimize treatment in the first- and second-lines. Crizotinib and entrectinib are the first 2 frontline options, but others may be active in the refractory setting.

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Benjamin P. Levy, MD, discusses biomarkers that have led to the development therapies with high response rates in lung cancer.

Targeted Therapies Show Activity in ROS1 Fusion-Positive Lung Cancer

Benjamin P. Levy, MD, an associate professor at Johns Hopkins School of Medicine and clinical director for the Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses the role of biomarkers in the treatment landscape for patients with lung cancer.

More recently, physicians have gotten a firmer understanding of the genomic underpinnings of tumors, says Levy. This began with EGFR mutations and moved toward the ALK mutations. Most recently, Levy says we have learned there are other actionable mutations in lung cancer besides EGFR and ALK.

Other driver mutations in lung cancer induce RET rearrangements, NTRK fusions, and MET exon 14 skipping mutations. These are important for identifying appropriate genotype-directed therapies for patients with lung cancer.

In nonsmall cell lung cancer in particular, this is not a one-size-fits-all model, Levy notes. Patients should be categorized into distinct genomic subsets in which particular targeted therapies are known to outperform chemotherapy, he concludes.

Benjamin P. Levy, MD, discusses the role of biomarkers in the treatment landscape for patients with lung cancer.

Biomarkers Evolve for Treatment of Lung Cancers

Benjamin P. Levy, MD, clinical director of medical oncology and associate professor of oncology at Johns Hopkins Sidney Kimmel Cancer Center in Sibley Memorial Hospital, Washington, DC, discusses the evolution of molecular drivers in nonsmall cell lung cancer (NSCLC) over the last few years and which testing should be included in patients with NSCLC.

Levy says research has come a long way in terms of the molecular driver identification in NSCLC. Initially, it started with testing for

in patients with advanced adenocarcinoma of the lung, but now there are a number of mutations that we can test for, including&nbsp;

If these mutations are identified, patients can be treated with a targeted therapy that has been approved by the FDA or is under the umbrella of a clinical trial.

The list continues to grow in terms of actionable mutations that should be tested for, Levy says. He says this is a call for comprehensive genomic profiling for lung cancer. More testing should be done outside of sequential

. Larger panels can be used to identify all of the mutations necessary at this time to improve outcomes for patients with NSCLC harboring 1 of these mutations.

https://www.targetedonc.com/conference/nylung-2019/expert-reviews-evolving-treatment-standards-for-nondriver-and-molecularly-driven-nsclc

Benjamin P. Levy, MD, discusses the evolution of molecular drivers in non&ndash;small cell lung cancer over the last few years and which testing should be included in patients.

The Role of Molecular Driver Identification Continues to Expand in NSCLC

Benjamin P. Levy, MD, an assistant professor of oncology and the clinical director of Medical Oncology at Sidney Kimmel Cancer Center and Johns Hopkins Medicine, discusses the evolution of liquid biopsies in all solid tumors, especially in nonsmall cell lung cancer (NSCLC) where they are used routinely.

Historically, Levy says liquid biopsies were initially used to detect resistance to EGFR targeted therapies, but more recently, 2 data sets demonstrated their utility in addition to tissue biopsies in patients with advanced NSCLC. In breast cancer and gastrointestinal (GI) malignancies, some utility for liquid biopsies has been demonstrated recently, but it has not been as ironed out as it has been in lung cancer.

Benjamin P. Levy, MD, discusses the evolution of liquid biopsies in all solid tumors, especially in non&ndash;small cell lung cancer (NSCLC) where they are used routinely.

Discussing the Evolution of Liquid Biopsies in Lung and Other Cancers

Benjamin P. Levy, MD, clinical director of Medical Oncology at John Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses genotyping in lung cancer, particularly focusing on

rearrangements are highly actionable, according to Levy. Crizotinib (Xalkori) has been approved by the FDA for

rearrangements, but there are many new drugs coming down the pike that are also active, including entrectinib. The next step with these drugs is determining the best sequence, while also understanding the mechanisms of resistance to ROS1, Levy says. Currently, crizotinib is still the standard, though Levy argues that the data from the World Conference on Lung Cancer shows entrectinib may also be considered.

Levy also discusses a recent tissue agnostic basket trial that investigated larotrectinib (LOXO-101) in patients with

fusions. The response rate in this trial was almost 70%. This drug has been exceptionally well tolerated and is the poster child for precision medicine, Levy says.

Benjamin P. Levy, MD, clinical director of Medical Oncology at John Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses genotyping in lung cancer, particularly focusing on&nbsp;<em>ROS1&nbsp;</em>and&nbsp;<em>TRK&nbsp;</em>mutations.

Investigating ROS1 and TRK Rearrangements in Lung Cancer

Benjamin P. Levy, MD, clinical director of Medical Oncology at John Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses the unique adverse events (AEs) with immunotherapy agents and how physicians can work together to overcome these challenges.

The therapeutic algorithms have changed with the use of immunotherapy, especially in lung cancer, Levy says. The AEs found with immunotherapy agents can affect any organ and can be T cell-, antibody-, or cytokine-mediated.

While a lot of the pathophysiology has been ironed out, physicians should still be wary of the side effects that can arise in their patients. Levy encourages physicians to collaborate with a multidisciplinary team and take a proactive approach with these AEs.

Benjamin P. Levy, MD, clinical director of Medical Oncology at John Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, discusses the unique adverse events with immunotherapy agents and how physicians can work together to overcome these challenges.

Benjamin P. Levy, MD | Authors

Articles

Targeted Therapies Show Activity in ROS1 Fusion-Positive Lung Cancer

Biomarkers Evolve for Treatment of Lung Cancers

The Role of Molecular Driver Identification Continues to Expand in NSCLC

Discussing the Evolution of Liquid Biopsies in Lung and Other Cancers

Investigating ROS1 and TRK Rearrangements in Lung Cancer

Understanding the Unique Adverse Events Associated With Immunotherapy Agents