Within-trial economic analysis of chemotherapy for high-risk early breast cancer informed by a 50-gene assay: 2-year results from the OPTIMA randomised trial

OPTIMA

Patient / Population Intervention / Exposure Comparison Outcome

In patients aged 40 or older with ER-positive HER2-negative early breast cancer and 0-9 involved nodes, chemotherapy directed by the 50-gene Prosigna assay improved quality-adjusted life-years and net health benefit over 2 years at a similar cost compared with chemo-endocrine therapy for all.

N

3,425patients

Design

Randomised trial (ISRCTN42400492) of participants aged ≥40 with ER-positive HER2-negative early breast cancer and 0-9 involved nodes, assigned to chemo-endocrine therapy or 50-gene Prosigna Risk of Recurrence (ROR)-directed therapy (chemo-endocrine if ROR >60, endocrine alone if ≤60), with a prespecified within-trial economic evaluation from the UK NHS perspective in 3,425 per-protocol participants (1,697 control, 1,728 test-directed).

Endpoint

Incremental costs (2025 GBP) and quality-adjusted life-years (EQ-5D-3L, area under the curve) over 2 years, and incremental net health benefit at £20,000 and £30,000 per QALY.

ResultMean 2-year cost £16,460 with test-directed therapy vs £17,111 with chemo-endocrine therapy, adjusted difference -£654 (95% CI -£1,525 to £218). Mean QALYs 1.47 vs 1.42, adjusted difference 0.05 (0.02-0.08). Incremental net health benefit 0.08 QALYs (0.03-0.13) at £20,000 and 0.07 (0.03-0.11) at £30,000 per QALY, with 100% probability of cost-effectiveness at both thresholds. 32% of the test-directed arm had chemotherapy. Chemotherapy costs £1,796 vs £5,540, difference -£3,611 (-3,800 to -3,422), against a 50-gene assay cost of £1,955. Ovarian suppression costs £2,438 vs £1,937, difference £487 (470 to 504).

Hall PS, Smith AF, McCabe C, et al. Presented at ESMO Congress 2026, abstract LBA86, 25 October. Not yet published.

Discussion & critique

This prespecified within-trial analysis found that test-directed treatment, with 32% of the arm receiving chemotherapy, gained 0.05 QALYs and had a positive net health benefit at both thresholds, because the chemotherapy it avoided cost more than the £1,955 assay. The cost saving has a 95% CI that includes zero, so the claim of dominance depends on the QALY gain, and 2 years is short compared with the 5-year IBCFS outcome, with the lifetime decision model still in progress. The analysis is per-protocol rather than intention-to-treat, QALYs come from self-reported EQ-5D-3L while the abstract does not say whether anyone was blinded, and it does not report how much data had to be imputed. The costs are specific to the UK NHS at 2025 prices, and the abstract does not explain why abemaciclib and ovarian suppression cost more in the test-directed arm.