Germline Testing and Somatic Tumor Testing for BRCA1/2 Pathogenic Variants in Ovarian Cancer: What Is the Optimal Sequence of Testing?

Abstract

Purpose: 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 (PV) should have somatic tumor testing to determine eligibility for a poly (ADP-ribose) polymerase inhibitor. Consequently, the majority of patients with ovarian cancer will have both germline testing and somatic testing. An alternate strategy is tumor testing first and then germline testing if there is a PV in the tumor and/or significant family history. The objective was to conduct a cost-effectiveness analysis comparing the two testing strategies.

Methods: The Markov model compared the costs (US dollars) and benefits of two testing strategies for newly diagnosed ovarian cancer: (1) ASCO strategy and (2) tumor testing triage for germline testing. Data were applied from SOLO-1, and costs were from wholesale acquisition prices, Medicare, and published sources. Sensitivity analyses accounted for uncertainty around various parameters. Monte Carlo simulation estimated the number tested and identified with germline and somatic BRCA PV for olaparib maintenance treatment annually in the US population.

Results: The ASCO strategy was more effective but more costly than tumor testing triage in identifying patients for olaparib, with an incremental cost-effectiveness ratio of $281,296 US dollars per progression-free life year gained. Assuming 10,000 eligible patients with ovarian cancer annually, Monte Carlo simulation yielded comparable numbers of patients with BRCA PV in the germline and tumor with the ASCO and tumor testing triage strategies (2,080 v 2,062, respectively), but substantially higher number of patients tested using the ASCO strategy (8,052 v 3,076).

Conclusion: The ASCO strategy may identify more BRCA PVs but is not cost-effective. Tumor testing in epithelial ovarian cancer as triage for germline testing is the favored strategy in this health care system.

FIG 1.

Two-way sensitivity analysis on costs of somatic tumor testing and olaparib (USD). PV, pathogenic variant; USD, US dollars.

FIG 2.

Sensitivity analysis on annual cost of olaparib (USD). USD, US dollars.

FIG 3.

Tornado diagram of model parameters and ICER. EV, expected value; ICER, incremental cost-effectiveness ratio; HGSC, high-grade serous carcinoma; PARP, poly (ADP-ribose) polymerase; USD, US dollars; WTP, willingness to pay.