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Broad genomic testing of NSCLC in community oncology disappoints

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Broad testing may still be warranted

There still may be a role for broad-based genomic testing in patients with NSCLC treated in community oncology practices, according to editorialists Paul A. Bunn Jr., MD, and Dara L. Aisner, MD, PhD. They discussed several study limitations that leave the matter unsettled.

Importantly, the majority of patients in whom this testing identified a potentially treatable alteration did not receive the treatment. “This gap between finding and treating molecular alterations in the community-based clinical setting highlights the reality that obtaining more tumor genomic information must be complemented with clinician education and decision support to understand the importance of matched therapy, and demonstrates a strength of harnessing EMR data to identify potential gaps in practice,” they maintain.

The study did not assess important outcomes other than survival, such as progression-free survival and response rate, Dr. Bunn and Dr. Aisner further note. Previous research has shown that tyrosine kinase inhibitors, for example, improve some of these outcomes without altering survival.

Another limitation was that the study period predated regulatory approval of some relevant targeted therapies and came shortly on the heels of approval of a targeted therapy for ALK rearrangements. And additional therapies are in the pipeline.

“[T]he incremental value of a cutoff of 30 genes analyzed may place the bar too high to appreciate a survival advantage and the tissue, time, and cost savings due to next-generation sequencing were not considered,” the editorialists point out. The optimal number of genes is unclear and likely to change over time.

Finally, the reports oncologists receive from broad-based genomic sequencing may be long and complex, which may deter them from pursuing appropriate therapy, Dr. Bunn and Dr. Aisner propose.

“The study… provides important insights into how broad-based genomic sequencing is used in the community oncology setting, where the majority of patients with advanced NSCLC in the United States receive care,” they conclude. “However, the limitations of this investigation suggest that the authors’ conclusion that broad testing is not warranted should be tempered to ensure that patients receive the right therapy for the right alteration at the right time.”

Paul A. Bunn Jr., MD, is with the University of Colorado Cancer Center and department of medical oncology, University of Colorado, Denver and Dara L. Aisner, MD, PhD, is with the University of Colorado Cancer Center and department of pathology, University of Colorado, Aurora. These comments were excerpted from an accompanying editorial .



The promise of broad-based genomic sequencing of advanced non–small cell lung cancer (NSCLC) to improve outcomes has not been realized in community oncology, results of a retrospective cohort study reported in JAMA suggest.

Investigators led by Carolyn J. Presley, MD, a thoracic and geriatric medical oncologist at the Ohio State University Comprehensive Cancer Center, Columbus, assessed outcomes among more than 5,500 patients with advanced nonsquamous NSCLC treated mainly in U.S. community practices. Overall, 15% had broad-based genomic testing (next-generation sequencing evaluating more than 30 cancer genes).

Main results showed that, among the patients having broad testing, less than 5% received a targeted treatment based on results that were not attainable with routine testing for common alterations in EGFR and ALK genes. Moreover, survival after broad testing was not better than that after routine testing.

“This study highlights how broad-based genomic sequencing has disseminated beyond traditional research settings ahead of a demonstrated association with better survival,” Dr. Presley and her coinvestigators write. They speculate that community uptake is being driven by the ease and cost of ordering a single comprehensive test, perceived benefit, attempts to conserve tissue, and hopes of improved survival if a targeted treatment is available.

“The lack of an association between broad-based genomic sequencing and survival is likely multifactorial,” the investigators maintain. “First, there were few genetic alterations identified with available targeted treatments. Second, even among those patients for whom targeted treatments were available, the treatments may not yield a substantial survival benefit or patients may not have had access to targeted agents due to financial barriers. Decision support for clinicians once they receive broad-based genomic sequencing results may also be needed.”

Study details

Dr. Presley and colleagues used the Flatiron Health Database to identify patients with advanced NSCLC who received care at 191 oncology practices across the United States during 2011-2016. The 5,688 patients studied had stage IIIB, stage IV, or unresectable nonsquamous NSCLC and received at least one line of treatment.

Overall, 15.4% received broad-based genomic sequencing of their tumor, while the rest received routine testing for EGFR and/or ALK alterations only, according to the results reported.

In the broadly tested group, merely 4.5% were given targeted treatment based on testing results. Another 9.8% received routine EGFR/ALK-targeted treatment, and 85.1% did not receive any targeted treatment.

The 12-month unadjusted mortality rate was 49.2% for patients undergoing broad testing, compared with 35.9% for patients undergoing routine testing.

In an instrumental variable analysis done to account for confounding, the 12-month predicted probability of death was 41.1% after broad testing and 44.4% after routine testing (P = .63).

Findings were similar in a propensity score–matched survival analysis (42.0% vs. 45.1%; hazard ratio, 0.92; P = .40), although there was some suggestion of a benefit of broad testing over routine testing in a Kaplan-Meier analysis among the entire unmatched cohort (HR, 0.69; P less than .001).

“Improved access to research clinical trials in the community setting may improve use of mutational data,” the investigators speculate. “Given the paucity of targeted agents, efforts to increase access to broad-based genomic sequencing should be paired with efforts to facilitate clinical trial enrollment.”

Dr. Presley disclosed that she receives grants from the Yale Lung SPORE Career Development Award, the Robert Wood Johnson/Veterans Affairs Clinical Scholars Program, and The Ohio State University K12 Training Grant for clinical faculty investigators. The study was funded by the Veterans Affairs Robert Wood Johnson Clinical Scholar Program and the Yale Lung SPORE Career Development Award.

SOURCE: Presley CJ et al. JAMA. 2018 Aug 7. doi: 10.1001/jama.2018.9824.

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