Abstract Background: Novel drugs for metastatic breast cancer (mBC) can provide patients not only improved survival but also the opportunity to benefit from future treatment innovations, a concept referred to as real option value (ROV). A recent study indicated that 68% of oncologists consider ROV when making treatment recommendations, but relatively few studies have quantified ROV. Extended survival follow-up from the OlympiAD study suggested a greater survival benefit with olaparib compared to chemotherapy in the subset of patients treated in the first-line (1L) setting. Given the rapid pace of innovation for human epidermal growth factor receptor 2 (HER2)-negative mBC, quantifying the ROV of 1L olaparib may help clinicians and patients better understand the impact of utilizing innovative therapies in earlier lines when appropriate. Objective: To quantify the ROV of olaparib for 1L treatment of hormone receptor-positive (HR+)/HER2-negative and triple negative metastatic breast cancer (TNBC) patients with germline BRCA1,2 pathogenic mutations. Methods: We developed a Markov model consisting of progression-free, progression, and death health states to estimate the quality-adjusted survival gain of 1L olaparib vs. treatment of physician’s choice (TPC, i.e. chemotherapy). To derive ROV, a scenario without future drug innovation, estimated by extrapolating the extended survival follow-up OlympiAD 1L data, was compared to one considering anticipated future innovations as of January 2023 (date of trial publication). Key ROV parameters were derived from literature, previous clinical trial data, ongoing studies as of January 2023, previous oncology clinical trial success and timing, and mBC treatment patterns. ROV parameters and survival curves were input separately for HR+ and TNBC due to inherent clinical differences between the two subpopulations. Parameter assumptions were reviewed by experts and assigned values to generate high-, mid-, and low-ROV scenarios; parameters included future innovation effect size (hazard ratios of 0.65, 0.75, and 0.85 for HR+ and 0.4, 0.6, and 0.7 for TNBC), timing of access to innovative therapies (4, 6, and 8 months for HR+ and 1, 4, and 6 month(s) for TNBC), probability of approval success (40%, 60%, and 80%), and rate of uptake (50%, 70%, and 80%). The primary outcome was aggregated quality-adjusted survival, weighted between HR+ and TNBC according to the OlympiAD trial characteristics. Results: Without future innovation, aggregate (weighted across HR+ and TNBC) quality-adjusted survival for olaparib was 23.3 vs. 12.8 months with TPC (10.5 additional months). With innovation, survival increased to 27.4 and 16.2 months (Δ11.2 months) in the high-scenario with olaparib and TPC, respectively (increase of 0.7 months vs. no innovation); 24.8 and 14.0 months (Δ10.8 months) (increase of 0.3 months vs. no innovation) in the mid-scenario; and 23.8 and 13.1 months (Δ 10.7 months) (increase of 0.2 months vs. no innovation) in the low-scenario. ROV thus yielded a relative increase in quality-adjusted survival with olaparib vs. TPC of 6.1%, 3.2%, and 1.0% in each scenario, respectively. Conclusions: Treatment with 1L olaparib likely improves a patient’s opportunity to benefit from future treatment innovations by extending progression free and overall survival. These findings can inform clinical decision-making by guiding early treatment selection to optimize treatment sequencing and positioning, and support further studies that evaluate the ROV of additional guideline-recommended treatments in mBC. Citation Format: C. L. Gong, M. Chavez-MacGregor, D. Elsea, X. Xu, L. Park, S. Katsandres, K. Migliaccio-Walle, D. L. Veenstra. The value of innovation in breast cancer treatment: Real Option Value of Olaparib for First-Line Treatment of gBRCA1,2 Pathogenic Mutation HR+/HER2-negative and Triple Negative Metastatic Breast Cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-11-03.
Gong et al. (Tue,) studied this question.