Abstract PS2-06-12: Quantifying the Minimum Acceptable Benefit for a Novel Oral Adjuvant Therapy in HR+/HER2− Early Breast Cancer: A Probabilistic Threshold Technique Study in Italy

Abstract Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer (BC) is the most frequently diagnosed BC subtype. In HR+/HER2- early breast cancer (eBC), adjuvant endocrine therapy (ET) - administered after surgery, with or without radiotherapy or chemotherapy - is the standard of care to reduce recurrence risk. Recently, combining ET with cyclin-dependent kinase 4/6 inhibitors has emerged as a new adjuvant strategy for patients with HR+/HER2− eBC. As adjuvant therapy aims to prevent recurrence rather than cure, understanding patients and clinicians’ preferences regarding risk-benefit trade-offs in this setting is critical. This study uses a probabilistic threshold technique (PTT) to estimate the minimum additional benefit (MAB) in 5-year invasive disease-free survival (iDFS) required by Italian patients and clinicians to prefer a novel oral adjuvant therapy over the current standard of care. Methods: The PTT questionnaire, simplified in wording for patients, was structured around a reference and a target option described by six attributes, whose levels were based on published data. The reference option reflected the profile of endocrine therapy (ET) alone, while the target option of ribociclib plus ET (Table 1). Respondents were blinded to the real-world identity of these treatments, labeled in the questionnaire as Treatment A and B. The key attribute (5-year iDFS) was initially set at 72% for both alternatives based on the efficacy of the reference option and its value varied iteratively for the target option at each question, until the respondent changed their initial choice or was indifferent between the two alternatives. Descriptive statistics were used to analyze responses. Results: A total of 112 clinicians and 99 patients were included in the final analysis. Clinicians required an average increase in iDFS of 5.17 percentage points (p.p.) (SD=6.26), while patients required 6.40 p.p. (SD=7.98) to prefer the target over the reference; the difference between the two groups was not statistically significant (t-test, p=0.21). Furthermore, no significant differences were observed within each group based on relevant personal characteristics. Median MAB was 4.50 p.p. for clinicians and 4.00 p.p. for patients. Patient preferences were more polarized: 33.3% accepted a MAB ≤1 p.p., while 25.3% required >10 p.p., compared to 25.0% and 12.5% of clinicians, respectively. Conclusion: The analysis provides quantitative insights into how Italian patients and clinicians evaluate risk-benefit trade-offs of novel adjuvant therapies for HR+/ HER2- eBC. While average MAB are similar, patient preferences are more polarized, ranging from very low to very high efficacy thresholds. This heterogeneity reinforces the need for shared decision-making that incorporates individual patient values. Citation Format: A. Zambelli, R. Berardi, B. Canali, R. Mercati, A. Messi, M. Suter, I. Viganò, D. Valsecchi, G. Arpino. Quantifying the Minimum Acceptable Benefit for a Novel Oral Adjuvant Therapy in HR+/HER2− Early Breast Cancer: A Probabilistic Threshold Technique Study in Italy [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 PS2-06-12.