OBJECTIVES: The objective of this analysis was to evaluate the impact of sequencing versus point mutation testing on outcomes in non-small cell lung cancer (NSCLC) using real-world data (RWD). Over time, there has been a shift in recommendations from single-gene or small-panel testing to broader genomic profiling with next-generation sequencing (NGS). In 2018, The Centers for Medicare and Medicaid Services (CMS) established the first national coverage for NGS for NSCLC. Since then, both CMS and compendial recommendations have continued to evolve, with increasing emphasis on NGS. This analysis sought to understand how these changes in testing practices might impact patient outcomes.

METHODS: The study included 877 patients with a median age of 66, and about 37% of patients underwent sequencing testing before first-line/adjuvant treatment (28%) or in relation to second-line treatment (9%). The study had two endpoints: median progression-free survival on second-line treatment (mPFS2) and hazard ratio (HR) of progression on second-line treatment. Statistical analysis involved pairwise comparisons of survival distributions (time to progression) and testing using logrank test statistics.

RESULTS: The results did not show a significant difference in HR or mPFS2 between patients who underwent sequencing versus non-sequencing testing for NSCLC. However, for patients with clinically relevant aberration, the sequencing arm showed an apparent benefit with longer mPFS2 on first-line treatment (14.5 vs 12.8 months), although not statistically significant. Similarly, sequencing testing performed early appeared to provide an apparent benefit in terms of mPFS2 (36.7 vs 35.2 months), although not statistically significant.

CONCLUSIONS: Overall, the study showed an apparent albeit statistically non-significant benefit for sequencing in patients requiring targeted therapy and in performing a sequencing test early. The results suggest that while sequencing testing may have potential benefits in some patients, further research is needed to better understand its role in guiding treatment decisions for NSCLC.