Broad-based genomic screening benefits questioned for advanced NSCLC
medwireNews: Most patients being treated in the community setting for advanced nonsquamous non-small-cell lung cancer (NSCLC) do not benefit from the use of broad-based genomic sequencing, suggests a study comparing this approach with routine testing for only epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) alterations.
“[B]road-based genomic sequencing directly informed treatment in a minority of patients and was not independently associated with better survival”, say Carolyn Presley, from The Ohio State University in Columbus, USA, and co-workers in JAMA.
The team collated information from the Flatiron Health Database for 5688 patients with stage IIIB/IV, or recurrent or progressive early-stage NSCLC who underwent treatment and genetic analysis at one of 191 oncology practices across the USA between 2011 and 2016.
The majority (84.6%) received routine testing, all of whom were examined for EGFR mutations and 94.5% were tested for ALK status. The remaining 15.4% of patients instead underwent screening using any panel that examined for variants in more than 30 genes, commonly including ROS1, KRAS, and PD-L1.
Patients who received immunotherapy were a significant 2.48 times more likely to undergo broad-based genomic screening than those who did not, after adjusting for confounders such as age, sex, stage and smoking status. And in turn, use of immunotherapy within the first four lines of therapy significantly predicted better survival, with an adjusted hazard ratio of 0.41, the researchers say.
But while the unadjusted 12-month mortality rate was significantly higher among the routine testing group than their broad-based screening counterparts (49.2 vs 35.9%), instrumental variable analysis found no significant difference between the predicted probability of death by 12 months (44.4 vs 41.1%).
And the lack of association between broad-based screening and overall survival was confirmed in a further propensity score-matched survival analysis of 1038 patients, the team emphasizes.
Just 4.5% of the patients who underwent broad-based genomic screening received a targeted therapy based on their test results, while 9.8% received EGFR- or ALK-targeted therapy, and 85.1% did not receive any targeted agent.
These findings “stand in contrast” to findings from studies of broad-based genomic screening use within clinical trials, say Presley et al, noting that these “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.”
However, the authors of an accompanying opinion highlight that only 36 of the 125 patients found to have targetable mutations using broad-based genomic screening received the relevant targeted therapy.
Paul Bunn Jr and Dara Aisner, from the University of Colorado, Denver, in Aurora, USA, also point out that the current study only assessed 12-month survival and therefore “likely underestimates other forms of benefit” resulting from targeted treatment based on broad-based genomic screening, such as progression-free survival, objective response rate or quality of life.
And they observe that the analysis predates the use of the newer tyrosine kinase inhibiters for EGFR and ALK alterations and agents targeting ROS1 and BRAF V600E mutations, as well as treatments currently under investigation for patients with RET or NTRK fusions or ERBB2 and MET mutations.
“[T]he study by Presley and colleagues 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”, the commentators write.
“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.”
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