Upfront Next-Generation Sequencing for Lung Cancer Patients Saves Time, Money

Use of upfront next-generation sequencing (NGS) testing at diagnosis of patients with metastatic non-small-cell lung cancer (mNSCLC) is associated with substantial cost savings, according to a study published in the JCO Precision Oncology. The authors say the findings hold true for patients covered by Medicare or commercial payers.

There are several currently approved therapies targeting EGFR, ALK, ROS1, and BRAF

V600E alterations, while targeted therapies for MET, HER2, NTRK1, and RET alterations are currently in clinical trials. Despite genetic testing becoming the standard of care for patients with lung cancer, the authors say that only a small percentage of patients with NSCLC currently receive NGS. Barriers include a lack of awareness of its benefits, limited coverage, and low reimbursement rates. So, the authors undertook an assessment of the economic impact of various genetic testing strategies to inform future policymaking.

“As more clinically relevant genetic targets in NSCLC emerge that require routine testing at diagnosis, it is vital to identify the molecular testing strategy that is timeliest, spares the most tissue, and is most cost efficient, as this must be done in every new patient,” write the authors led by Nathan A. Pennell, M.D., Ph.D., from the Cleveland Clinic in Ohio.

The researchers developed a model that evaluated four testing scenarios and assessed time to results, the proportion of patients identified with genetic alterations, and total testing costs. The four genetic testing scenarios included:

• Upfront NGS for EGFR, ALK, ROS1, BRAF, MET, HER2, RET, and NTRK1 (all alterations tested simultaneously) plus KRAS
• Sequential testing (sequence of single-gene tests)
• Exclusionary testing (KRAS plus sequential testing)
• Hotspot panels (EGFR, ALK, ROS1, and BRAF tested simultaneously plus single-gene tests or NGS for MET, HER2, RET, and NTRK1)

All four testing strategies included programmed death ligand 1 (PD-L1) and routine immunohistochemistry testing. The model assumed that in the case of insufficient tissue sample, a rebiopsy would be attempted, which may or may not be successful. Additional assumptions included that immunohistochemistry or fluorescence in situ hybridization tests would be used for ALK, ROS1, MET, RET, and NTRK1 testing, while real-time polymerase chain reaction would be used to perform KRAS, EGFR, HER2, and BRAF testing.

Costs were based on the 2017 Clinical Lab Fee Schedule for the Medicare-insured population (costs ranging from $180.20 for BRAF to $433 for HER2), while commercial costs were calculated using two U.S. administrative claims databases (ranging from $406 for BRAF to $1,127 for HER2). Multigene panels were reimbursed at $1,345 for Medicare and $3,299 for commercial payers, while NGS was calculated based on $627.50 and $2,860, respectively. Finally, PD-L1 was reimbursed at $433 and $1,127, respectively.

For both Medicare and commercial payers, the model assumed a hypothetical health plan covering 1,000,000 members (either 65 years and older or 18 to 65 years of age). This yielded and estimated 2,066 Medicare-insured patients and 156 commercially insured patients having mNSCLC and eligible for testing. Time-to-test results were 2.0 weeks for both NGS and the hotspot panel versus 2.7 and 2.8 weeks, respectively, for exclusionary and sequential testing. NGS was associated with cost savings for both Medicare and commercial payers. NGS yielded savings of $1,393,678 versus exclusionary testing, $1,530,869 versus sequential testing, and $2,140,795 versus hotspot panels for Medicare $3,809, $127,402, and $250,842, respectively, for commercial payers.

NGS identified all 446 of 2,066 Medicare-insured patients having alterations targetable by U.S. Food and Drug Administration- (FDA-) approved therapies, as well as all 34 of 156 commercially insured patients. This identified 2.3 percent to 5.9 percent more patients than other testing strategies. Further, NGS identified all 156Medicare-insured patients and all 12 commercially insured patients estimated to have alterations without FDA-approved therapies, identifying 32.2 percent to 43.7 percent more patients than other testing strategies.

The researchers say that increasing the proportion of NGS-tested patients translated into substantial cost savings for both CMS and commercial payers. By increasing the proportion of NGS-tested patients from 25 percent to 50 percent, Medicare would save $492,251 and a commercial payer $52,421.

“Our model illustrates that moving from sequential single-gene tests or even panels of tests to broader NGS testing for patients with advanced NSCLC is already the best strategy in these three areas and will only become more relevant as the list of tests grows,” the authors conclude. “Stakeholders should consider moving to NGS as the preferred method for biomarker testing.”

The study was funded by Novartis Pharmaceuticals.

Takeaway: Using NGS to target treatment in patients with newly diagnose mNSCLC yields both cost savings and speeds time to treatment initiation, compared to other testing strategies.