Benefits of broad-based sequencing questioned in NSCLC
medwireNews: Only a small minority of patients with advanced non-small-cell lung cancer (NSCLC) who undergo broad-based genomic sequencing subsequently receive targeted therapy, study findings indicate.
Furthermore, receipt of the broad-based test is not associated with significantly improved survival compared with routine testing for EGFR mutations and/or ALK rearrangements alone.
“These results stand in contrast to prior studies, which did not account for routine testing for EGFR and/or ALK as a comparison group, or use robust analytic techniques to account for both measured and unmeasured confounders,” Carolyn Presley (The Ohio State University, Columbus, USA) and co-investigators remark.
Presley and team reviewed data for 5688 individuals (median age, 67 years) with stage IIIB/IV, or recurrent or progressive early-stage, nonsquamous NSCLC who were treated in a community oncology setting. Of these, 15.4% received broad-based genomic sequencing, defined as any multigene panel sequencing assay examining more than 30 genes prior to third-line treatment, and 84.6% received routine testing.
As reported in JAMA, unadjusted mortality at 12 months from the start of first-line treatment was 49.2% for the patients who underwent genomic sequencing and 35.9% for those who underwent routine testing.
However, after adjusting for potential confounders, including a higher rate of immunotherapy in the former group (4.0 vs 1.7%), there was no significant association between broad-based genomic sequencing and 12-month mortality.
Specifically, the predicted probability of death at 12 months was 41.1% for broad-based genomic sequencing compared with 44.4% for routine testing. Similar results were observed in a propensity score-matched survival analysis of 1038 patients, with the 12-month probability of death at 42.0% and 45.1%, respectively.
The researchers note that the majority (88.9%) of patients who received broad-based genomic sequencing had a genetic mutation identified, most commonly TP53, KRAS, EGFR, CDKN2A, and STK11.
But just 4.5% received targeted treatment based on testing results. A further 9.8% received routine EGFR/ALK-targeted treatment, and 85.1% received no targeted treatment.
The most commonly targetable alterations, other than EGFR and ALK, were BRAF V600E, and MET and ERBB2 mutations.
Presley et al say there may be several reasons for the lack of association between broad-based genomic sequencing and survival, including a lack of targeted treatments for the genes identified and limited benefit of those treatments available, as well as financial constraints.
They conclude: “Use of broad-based genomic sequencing in the community setting for advanced non–small cell lung cancer may not currently offer a survival advantage.”
However, Paul Bunn and Dara Aisner, both from the University of Colorado in Denver, USA, write in an accompanying editorial that the study should not cause people to think that “broad-based genomic sequencing should be avoided in nonsquamous NSCLC.”
They say that the gap between finding and treating molecular alterations seen in this study highlights a need for improved understanding of the importance of matched therapy, and that only looking at 12-month survival “likely underestimates other forms of benefit in broad-based genomic sequencing–driven targeted therapy,” such as objective response rate and progression-free survival.
The editorialists also note that since the study was completed a number of new drugs targeting mutations in genes such as ROS1 and BRAF have been approved. Lack of availability of these therapies may have resulted in “study bias against broad-based genomic sequencing,” they remark.
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group