Clinicians Still Unaware of Need for Genetic Testing in NSCLC

Pam Harrison

May 28, 2020

An international survey sent to clinicians who treat nonsmall cell lung cancer (NSCLC) has found that one third were unaware of evidence-based guidelines that recommend targeted therapies when a driver mutation is identified.

Moreover, the majority of these clinicians believe that fewer than 50% of patients in their country undergo molecular testing, the same survey showed.

The survey was conducted by the International Association for the Study of Lung Cancer (IASLC); 2537 questionnaires from 102 countries were returned and analyzed.

It was published online May 20 in the Journal of Thoracic Oncology.

The results are concerning because "the risk of death for patients with NSCLC is substantially reduced when a gene alteration is identified and the available targeted therapy is administered," the authors emphasize.

"Specific protocols to initiate reflex testing for guideline-recommended molecular markers would help providers consider molecular testing earlier and optimize tissue," they suggest.

Surprised That Clinicians Were Unaware of Guidelines

"I was not surprised that we found suboptimal testing rates based on other research that has demonstrated the need to improve the quality of lung cancer in some areas," corresponding author Matthew Smeltzer, PhD, University of Memphis, Tennessee, told Medscape Medical News in an email.

"However, I was surprised that so many respondents were unaware of guidelines," he said.  

The College of American Pathologists, IASLC, and Association for Molecular Pathology established evidence-based standards for the selection of NSCLC patients for molecular testing in 2013, and these guidelines were subsequently endorsed by the American Society of Clinical Oncology.

"We suspect that the level of access a provider has to targeted therapies does affect molecular testing rates," Smeltzer acknowledged. 

Molecular Testing Survey

"The survey included a seven-question introduction for all respondents and then divided respondents into one of three tracks," the authors explain.

These tracks included respondents who requested tests and who treated patients (medical oncologists), those who analyzed and interpreted assays (pathologists), and those who acquired tissue samples (surgeons, pulmonologists, radiologists).

Countries were also grouped into five geographic regions — Asia, Europe, Latin America, United States, and Canada — and the rest of the world (ROW).

"Overall, respondents reported that molecular testing rates were lower than we would like but they were not satisfied with the current state of testing, and they reported higher testing rates in their own clinics," Smeltzer noted.

However, when tests were ordered, "we found 99% of respondents in the requesting/treating track ordered tests for EGFR, 95% for ALK, 79% for ROS1, and < 50% ordered other tests," the authors observe.

Indeed, EGFR, ALK, and ROS1 were the top three tests ordered across all regions, though less frequently so in the ROW, they add.

More than half of requesting/treating track respondents also order multiplex assays, although Latin America and the ROW did this less frequently than other regions.

Over 90% of respondents who perform or interpret assays indicated that they perform EGFR testing, while 83% of the same group do ALK testing; 69% tested for KRAS; 68% for BRAF, 64% for ROS1, and 56% for HER2. Fewer than half of them performed other tests.

Survey results also showed that EGFR, ALK, and KRAS are the top three tests performed across all regions, with no regional differences.

"Respondents also reported on the acquisition and testing of liquid biopsies," survey authors point out.

Here, 87% of requesting/treating track respondents indicated that they "sometimes" request molecular testing on liquid biopsies, but the proportions of those who sometimes use liquid biopsy varied by region and were lowest in Latin America and the ROW.

A lower proportion of those who perform and interpret assays, at 69%, also offer tests on liquid biopsies, but this percentage, too, varied significantly by region, being the least frequently done in the United States and Canada as well as in the ROW.

All the above tests are for genetic mutations or alterations that guide clinicians on use of targeted therapy directed at particular mutations, for example, drugs like erlotinib for EGFR and crizotinib for ALK.

However, immunotherapy with checkpoint inhibitors has also made a big impact on the treatment of NSCLC, and the use of these agents is sometimes guided by testing for programmed cell-death ligand (PD-L1).   

PD-L1 is not a molecular marker per se, the authors note.

Nevertheless, "we found that 84% of respondents in the requesting/treating track ordered PD-L1 and 68% of respondents who perform or interpret assays report PD-L1 is offered in their own lab," the authors observe.

Smeltzer commented that both approaches — targeted therapies and immunotherapy — have made inroads into the treatment of NSCLC, in some cases replacing chemotherapy.

He emphasized that "it is important to know if a specific oncogene driver is present before initiating immunotherapy treatment," and noted that when tissue is sent out for both types of testing, the results for PD-L1 are usually available before the results for the full molecular testing panel are back.

Barriers to Testing

"The most frequent barrier to molecular testing in every region was cost," the survey authors note.

Insufficient amount of tumor cells was the main reason for molecular testing failures along with inadequate tissue quality.

The majority of respondents who order tests and treat patients were sure that the laboratories they use perform appropriate validation of molecular tests, while almost all of those who perform or interpret assays said they perform validation tests in their labs.

Only 30% of respondents who request tests and treat patients have access to molecular testing labs within their own institutions, the remaining respondents have to outsource testing completely or partially.

Most respondents who test and treat patients also have multidisciplinary tumor boards to discuss patients with NSCLC, but almost one quarter of the same group indicated their board met less than once a month.

"Turnaround time is a barrier to molecular testing across the world," the authors continue, with 29% of those who request tests and treat patients reporting that it typically takes 10 days or more to receive molecular testing results.

Interestingly, the highest percentage of respondents who reported this long turnaround time were in North America.

Perhaps encouragingly, 41% of respondents who perform or interpret assays indicated they were dissatisfied with the condition of molecular testing in their country, although in this regard, the United States and Canada had the lowest rates of dissatisfaction.

In fact, 39% of those who request tests and treat patients ranked the conditions of molecular testing in their country as "average or below" while 42% of respondents in the tissue acquisition track ranked the conditions of molecular testing as average or below, the worst rankings coming from Latin America and the ROW.

Low quality of tissue samples was another reason respondents expressed dissatisfaction with the current state of molecular testing in their country.

Smeltzer is a research consultant for the Association of Community Cancer Centers.

J Thorac Oncol. Published online May 20, 2020. Full text

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