In a lively discussion at the European Lung Cancer Conference, Prof. Frances A. Shepherd (University of Toronto) argued in favor of upfront next generation sequencing (NGS) while Prof. Keith M. Kerr (Department of Pathology, Aberdeen University Medical School) defended a more conservative approach to testing.
Why this matters
NGS is no longer confined to research and clinical studies but assumes an important role as a diagnostic tool that helps guide treatment decisions.
- Pathology samples should be handled only once.
- Pulling archived specimens is expensive and costs time.
- The time to give adjuvant treatment based on genetic profiles is now (PD-L1 inhibitors, EGFR TKIs etc.)
- Tumors are temporarily heterogenous and may be molecularly different, so sampling earlier makes missing a specimen less likely. Resistance mutations emerge AFTER treatment.
- ESMO guidelines address which genes to test for, what methods etc, but they don´t say when.
- Not all mutations that can be tested are approved, and many are restricted to certain indications or subpopulations of patients (eg, some EGFR, ALK, or ROS1 mutations in smokers).
- Guidelines differentiate between a minority of tests that should be done, and many more that can be done.
- A lot of potential targets do not have approved drugs behind them.
- The cost of NGS (in the US) is around $1000, which can be more than 10 times as much as other methods (IHC, FISH, PCR).
- Turnaround time for NGS is 5-14 days, while other methods may be much faster.
- “The moment you learn to separate your wants from your needs, your vision becomes clearer.”
Consulting or honoraria - Shepard FA: AstraZeneca, Roche, BI, Novartis, Pfizer and AZ stock. Kerr KM: AbbVie, Archer Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ventana.