David R. Gandara, MD, Director, Thoracic Oncology Program, University of California, Davis Comprehensive Cancer Center, discusses factors that help determine which patients with lung cancer should be tested for molecular aberrations.

Gandara believes that the best approach for determining whom to test is still debatable. However, new guidelines from IASLC and CAP recommend that all patients with adenocarcinoma should be tested for molecular abnormalities.

For EGFR and ALK aberrations, it has been suggested that the most cost-effective approach involves testing only never-smokers who have adenocarcinomas. However, Gandara explains that many former or light smokers are testing positive. The increasing frequency of these reports confirms the recommendations within the guidelines to test all patients with adenocarcinoma.

Moreover, Gandara notes that some patients with squamous cell carcinoma are also exhibiting ample actionable abnormalities that warrant molecular testing.

Videos

Dr. David Gandara from the UC Davis Comprehensive Cancer Center on Patient Selection for Molecular Testing in Lung Cancer

Dr. Gandara on Patient Selection for Molecular Testing

David R. Gandara, MD, Director, Thoracic Oncology Program, University of California, Davis Comprehensive Cancer Center, discusses the different types of molecular testing procedures available for patients with non-small cell lung cancer (NSCLC).

Several driver mutations and molecular abnormalities play an important role in determining the most appropriate therapy, for patients with NSCLC. Traditionally, testing for these aberrations has been done sequentially; however, a newer method known as multiplexing measures for several abnormalities simultaneously, in a single assay. Gandara notes that multiplexing is more cost effective, better utilizes the biopsy, and avoids the long delays that may accompany sequential testing.

 mutations, as an example of the benefits of multiplexing. In the past, KRAS status was used primarily to assess sensitivity to erlotinib or chemotherapy. Currently, there are classes of agents being investigated, such as MEK inhibitors, which are active in patients with 

 mutations. Knowing the status of KRAS early in the treatment process may guide the decision to enroll the patient in a clinical trial. Multiplexing allows physicians to assess KRAS status at the same time as other biological markers.

Dr. David Gandara, from  University of California, Davis Comprehensive Cancer Center, discusses using the multiplexing assay for patients with non-small cell lung cancer

Dr. Gandara Discusses Molecular Testing for NSCLC

David R. Gandara, MD, Director, Thoracic Oncology Program, University of California, Davis Comprehensive Cancer Center, discusses a database analysis conducted by the Southwest Oncology Group (SWOG) that examined the possible connection between thymidylate synthase (TS) expression and ALK-positivity in patients with non-small cell lung cancer (NSCLC).

A connection between ALK-positive NSCLC and TS, a predictive marker for sensitivity to the chemotherapeutic agent pemetrexed, could impact the way that patients with ALK-positive NSCLC are treated.

In order to establish a connection, the study examined 1,761 patients with lung adenocarcinoma that did not have an 

 mutation, from the Response Genetics Inc. (RGI) database. In total, 63 of the patients were ALK-positive and 1698 were negative. The median TS RNA level for patients with an ALK-positive tumor was 2.02 compared to 3.32 for ALK-negative. In general, TS levels less than 2.33 denote sensitivity to pemetrexed.

Gandara believes that this analysis provides a biologic rationale for the reports that pemetrexed is active in ALK-positive NSCLC. Following the positive results of the proof of concept analysis, SWOG plans to conduct a larger randomized trial that will provide patients with ALK-positive NSCLC either pemetrexed alone or in combination with the ALK-targeted agent crizotinib (Xalkori).

Dr. David Gandara, from UC Davis Cancer Center, on Thymidylate Synthase Expression in ALK-Positive Non-small Cell Lung Cancer

David R. Gandara, MD

Articles

Dr. Gandara on Patient Selection for Molecular Testing

Dr. Gandara Discusses Molecular Testing for NSCLC

Dr. Gandara on TS Expression in ALK-Positive NSCLC