Jean Lopategui, MD, associate professor of pathology and director of Translational Genomics and of the Molecular Genetics Pathology Fellowship at Cedars-Sinai, discusses the evolution of targeted therapies in non—small cell lung cancer (NSCLC).

Ten years ago, not many targeted therapies were available in the field, but there has been a tremendous improvement in the treatment of patients with NSCLC, says Lopategui. The 1-year mortality rate of stage IV NSCLC is about 50%. Today, patients who harbor molecular alterations can experience durable remissions due to the development of targeted therapies.

Additionally, checkpoint inhibitors could be a second-line treatment option after disease progression on targeted therapies or chemotherapy. These agents could further extend the lives of patients with NSCLC. Although these agents are not curative, it is encouraging to see the progress that has been made, concludes Lopategui.

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Jean Lopategui, MD, discusses the evolution of targeted therapies in non–small cell lung cancer.

Dr. Lopategui on the Evolution of Targeted Therapies in NSCLC

Jean Lopategui, MD, associate professor of pathology and director of Translational Genomics and of the Molecular Genetics Pathology Fellowship at Cedars-Sinai, discusses the evolution of molecular testing in non—small cell lung cancer (NSCLC).

Lung cancer, particularly NSCLC, has been the poster child for molecular testing, says Lopategui. The number of tests that are available to define and predict response to treatment is very high in this space. The field used to perform several tests in the past to categorize each of the genes and their mutations; this was time consuming and expensive, adds Lopategui. Today, next-generation sequencing is available, and this testing allows physicians to test multiple genes and mutations in just 1 test, concludes Lopategui.

Jean Lopategui, MD, discusses the evolution of molecular testing in non–small cell lung cancer.

Dr. Lopategui on the Evolution of Molecular Testing in NSCLC

Jean Lopategui, MD, associate professor of pathology and director of Translational Genomics and of the Molecular Genetics Pathology Fellowship at Cedars-Sinai, discusses the implications of genomic sequencing in lung cancer.

Patients with lung cancer should undergo molecular profiling to determine whether they could benefit from 

-directed therapy. Patients should undergo profiling upon diagnosis because some of these drugs, particularly for 

 mutations, are approved for frontline use, says Lopategui. Other drugs for patients with 

 exon 14 skipping mutations or amplifications, 

 mutations, and tumor mutational burden are in development, and are being explored in clinical trials, explains Lopategui.

Recently, entrectinib (Rozlytrek) and larotrectinib (Vitrakvi) received regulatory approval for the treatment of patients with solid tumors who harbor 

Dr. Lopategui on the Implications of Genomic Sequencing in Lung Cancer

Jean Lopategui, MD, associate professor of pathology and director of Translational Genomics and of the Molecular Genetics Pathology Fellowship at Cedars-Sinai, discusses the use of liquid biopsies in lung cancer.

Liquid biopsies are still an emerging technology, says Lopategui. While these tests are considered to be a less invasive alternative to tissue biopsies, the 2020 National Comprehensive Cancer Network guidelines state that liquid biopsies should only be used if a patient is medically unfit for an invasive tissue biopsy or if there is inadequate tissue for molecular analysis.

One of the drawbacks of liquid biopsies is the rate of false-negative results, says Lopategui. Plasma-based circulating tumor (ct)DNA and detection requires a very high sensitivity. However, the number of ctDNA copies in patient samples is not always high; this can lead to false negatives. As such, if a liquid biopsy is performed, a follow-up tissue-based analysis should also be done if an oncogenic driver is not identified, concludes Lopategui.

Jean Lopategui, MD, discusses the use of liquid biopsies in lung cancer.

Jean Lopategui, MD

Articles

Dr. Lopategui on the Evolution of Targeted Therapies in NSCLC

Dr. Lopategui on the Evolution of Molecular Testing in NSCLC

Dr. Lopategui on the Implications of Genomic Sequencing in Lung Cancer

Dr. Lopategui on the Use of Liquid Biopsies in Lung Cancer