Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Promise of broad genomic testing of NSCLC disappoints in community oncology

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

Key clinical point: In community oncology, broad-based genomic sequencing of NSCLC does not improve survival when compared with routine testing.

Major finding: The 12-month mortality rate was 49.2% for patients undergoing broad-based genomic sequencing and 35.9% for patients undergoing routine testing solely for EGFR and/or ALK alterations.

Study details: A retrospective cohort study of 5,688 patients with advanced nonsquamous NSCLC treated in 191 U.S. community practices.

Disclosures: 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.

Read the article.

Citation:

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

Commentary:

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 .