Exclusionary testing most efficient and cost-saving for NSCLC

Exclusionary testing, involving upfront testing for EGFR and ALK followed by next-generation sequencing (NGS) for other genomic alterations (GAs), is the most efficient and cost-saving molecular testing strategy for patients with metastatic non-small-cell lung cancer (NSCLC) in Hong Kong and perhaps East Asia, researchers from the Chinese University of Hong Kong (CUHK) have reported.

To compare costs, time to appropriate therapy, as well as actionable GAs (ie, EGFR, ALK, ROS1, BRAF, MET, and RET) and nonactionable GAs (ie, KRAS^G12C, NTRK1, and HER2) detected by sequential single-gene testing, hotspot panel testing, exclusionary testing, and upfront NGS in patients with metastatic NSCLC, the researchers developed a decision analytical model based on epidemiology data, testing and rebiopsy costs, and treatments approved in Hong Kong. The testing population included adult patients in Hong Kong with newly diagnosed metastatic NSCLC and unknown mutation/rearrangement status. Patients also received initial PD-1/PD-L1 screening at diagnosis, alongside the first GA testing modality. [JTO Clin Res Rep 2022;3:100290]

“Similarities in driver mutation epidemiology in East Asian countries indicate that the model can be used to represent patients with metastatic NSCLC throughout East Asia,” the researchers suggested. [Am J Cancer Res 2015;5:2892]

Results showed exclusionary testing, at a total cost of USD 6,535,487, was the cheapest testing modality, while NGS, at a total cost of USD 14,082,194, was the most expensive. Total cost savings with exclusionary testing were USD 3,871,105 vs sequential single-gene testing, USD 6,618,285 vs hotspot panel testing (simultaneous testing for all actionable GAs), and USD 7,546,707 vs NGS.

Exclusionary testing also yielded the shortest time to appropriate therapy for actionable GAs, at 1.6 weeks, compared with 2.0 weeks with hotspot panel testing and NGS, and 5.2 weeks with sequential single-gene testing.

“In the scenario where all patients used exclusionary testing, a cost saving of USD 4.6 million was expected relative to current practice, with 90.7 percent of actionable GAs and 46.5 percent of nonactionable GAs detected,” the researchers reported. “When all patients used NGS, it would be USD 2.9 million more expensive, with a 100 percent [actionable and nonactionable] GA detection rate.”

“Exclusionary testing is the best option in terms of cost and time-to-results in Hong Kong. This finding may be applicable to other Asian countries,” they concluded.

“On the basis of our model, positioning NGS after EGFR and ALK testing would be an attractive testing strategy to adopt, given its economic savings vs the current approach of sequential testing strategies,” they suggested.

However, upfront NGS would become cost-saving vs status quo at a 28 percent discount in NGS cost (ie, NGS cost at USD 2,320), and when all GAs become actionable with a 5.5 percent discount in NGS cost (ie, NGS cost at USD 3,044).

“Despite current recommendations and continued addition of new targeted therapies, the rate of molecular testing, including single-gene testing, in East Asian patients with NSCLC varies considerably, from as low as 42 percent in mainland China to 91 percent in Taiwan, meaning many patients are not receiving optimal treatment,” the researchers noted. [Am So Clin Oncol Edu Book 2019;39:531-542]

“Thus, there remains a considerable need to improve the implementation of efficient and cost-saving molecular testing strategies in East Asian clinical practice to meet guideline recommendations and ultimately improve patient survival,” they emphasized.