A study presented at the virtual 2021 ASCO Annual Meeting compared the cost-effectiveness of two testing strategies for patients with ovarian cancer.

“In 2020 ASCO recommended that all women with epithelial ovarian cancer have germline testing for BRCA1/2 mutations, and those without a germline pathogenic variant should have somatic tumor testing, to determine eligibility for PARP inhibitor therapy,” wrote Janice S. Kwon, University of British Columbia, Vancouver, BC, Canada, and colleagues.

“An alternate strategy is to start with tumor testing first, and to conduct germline testing only in those with a pathogenic variant in the tumor, or a significant family history,” they continued.

In order to compare the costs and benefits of the two testing strategies, Ms Kwon and colleagues used a Markov Monte Carlo simulation model.

A sufficient tissue sample for somatic tumor testing was available in 99% of cases, according to empiric data. Otherwise, the only option a patient would have is germline testing. The sensitivity of somatic tumor testing was 99% for detecting germline pathogenic variants. Only patients with a BRCA1 or BRCA2 pathogenic variant were eligible for PARP inhibitor therapy.

The primary outcomes measures were the number of patients eligible for PARP inhibitor therapy with progression-free life years (PFLYs) gained based on SOLO1 data and incremental cost-effectiveness ratio (ICER).

The Monte Carlo simulation estimated the number of patients who would have germline testing and somatic tumor testing, as well as the total number of patients with germline or somatic BRCA1 or BRCA2 pathogenic variant eligible for PARP inhibitor therapy.

The germline testing to somatic tumor testing strategy was more effective than a somatic tumor testing to germline testing strategy but was more costly ($111,115 vs $109,730, respectively). The incremental benefit from a germline testing to somatic tumor testing strategy would be achieved at substantial cost to the health care system, with an ICER of $119,340 per PFLY gained compared with the somatic tumor testing to germline testing strategy.

The results were highly sensitive to the sensitivity of somatic tumor testing to detect germline pathogenic variants, and the costs of germline testing and somatic tumor testing. Assuming that germline testing was less than 50% of the cost of somatic tumor testing, the sensitivity of somatic tumor testing had to exceed 98% for the somatic tumor testing to germline testing strategy to be cost-effective.

“Although the ASCO recommended strategy of BRCA germline testing followed by tumor testing for those without a pathogenic variant may be more effective in identifying ovarian cancer patients for PARP inhibitor therapy, it is more costly,” wrote Ms Kwon and colleagues.

“The ASCO strategy is justified if the sensitivity of tumor testing is not sufficiently high. However, assuming high tumor testing performance rates, tumor testing first followed by germline testing if there is a pathogenic variant in the tumor and/or family history is a cost-effective strategy,” they concluded.—Janelle Bradley

Kwon JS, Tinker A, Santos J, et al. Germline testing and somatic tumor testing for BRCA1/2 pathogenic variants in ovarian cancer: What is the optimal sequence of testing? Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 10585.