Next-generation sequencing (NGS): How often is testing performed too late?

Abstract

6575 Background: With the emergence of precision oncology over a decade ago, NGS and the utility of targeted therapies have readily been incorporated into standard-of-care (SOC) practices. Still in many cases, NGS is only done after patients (pts) have failed several lines of treatment and/or their performance status (PS) has declined. We aim to further evaluate the timing of NGS as it pertains to patients’ clinical disease course. Methods: All patients with incurable solid tumor malignancies undergoing NGS testing at our institution from January 2020 to December 2021 were included. Our genomics team (including medical oncologists, bioinformaticians, and a genetic counselor) routinely reviews all NGS results on a biweekly basis to assess for actionable alterations that would be eligible for on-label therapy (tx), clinical trials, and/or off-label consideration for targeted tx that has been FDA approved in another histology. Baseline demographics for pts such as age and gender, in addition to oncologic history, performance status, and date of death were collected via in-depth chart review utilizing the electronic medical record system. Results: We reviewed NGS results for 1767 pts, of which 1455 (82.4%) had genomic tumor board (GTB) recommendations for an actionable alteration. Of the 1767 pts, 33 were deceased at time of results review. The most common histology amongst the deceased were lower gastrointestinal tract (24.2%), genitourinary (18.2%), lung and pancreatic (15.2% each). At time NGS was ordered, 11 (33.3%) had received no prior tx, 8 (24.2%) had received one line of systemic tx, and 14 (42.4%) had received 2 or more lines of systemic tx. The average time from when NGS was ordered to results being reported was 17.9 days. The median time from when NGS was ordered to date of death was 26 days. At time NGS was ordered, 39% of pts had an ECOG PS of 0-1, 34% had an ECOG PS of 2, and 27% had an ECOG PS of 3-4. All 33 of these pts had actionable alterations for which GTB recommendations were made. All of these pts were matched to at least one clinical trial while 21.9% were recommended for an on-label tx as well. 54.5% of these pts were receiving care at regional facilities while 45.5% were receiving care at main campus. Conclusions: In our experience, all patients who were deceased at time of NGS review had an actionable alteration, for which there was a treatment recommendation made. In a rapidly evolving field where novel targeted therapies are on the rise, the rate of actionability is increasing, and NGS is now SOC, we are still seeing pts get testing done only after the receipt of multiple lines of systemic tx and/or once their PS has declined. These pts may benefit from earlier NGS testing, which would have opened up additional therapies earlier on in the course of their disease, when their PS was also likely to be more optimal. Further work is necessary to determine if early NGS testing makes a significant clinical impact on survival.