Abstract P5-01-08: Perceptions and behaviors of US oncologists treating HR-positive HER2-negative metastatic breast cancer in second-line

Abstract Background: The emergence of novel targeted therapies for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) offers more treatment options in second line (2L). While biomarkers can influence 2L treatment decisions, other factors such as comorbidities, co-occurring mutations, and treatment toxicities can guide treatment selection. Amid evolving treatments and clinical complexities, this interim analysis of an ongoing study aims to understand perception and behaviors of US oncologists in molecular testing and 2L treatment decisions in HR+/HER2- mBC with one or more PIK3CA, AKT1, or PTEN alterations. Methods: US oncologists completed a cross-sectional survey in April 2024 (interim analysis data cutoff 04-23-24). Recruitment quotas ensured diverse representation of oncologists from various practice settings. Qualitative concept elicitation and desk research informed survey development. The validity of the survey was assessed via cognitive interviews (N=8). Data were summarized with descriptive statistics. Results: This interim analysis included 152 oncologists (70 academic, 82 community), with mean 18.1 years in practice; 40.8% practiced in the Northeast. In the HR+/HER2- mBC setting, 77.6% of oncologists reported usually or almost always conducting next-generation sequencing (NGS) testing at diagnosis/prior to first-line (1L) treatment. Of patients not tested at diagnosis, 74.5% of oncologists reported usually or almost always conducting NGS testing prior to 2L treatment. When choosing 2L treatment for patients with HR+/HER2- mBC, most oncologists consider it was very important to know gBRCA (61.8%), ESR1 (57.2%), PIK3CA (55.3%), and/or PTEN (51.3%) status; fewer oncologists rated knowing AKT1 status as very important (42.8%). When presented with multiple actionable biomarkers, 68.4% of physicians selected PIK3CA mutation, AKT1 mutation, or PTEN alteration as more important for treatment choice than ESR1 mutation. Oncologists were asked to select 2L treatments for 12 patient profiles, which varied in age (44, 56, or 64 yr old), site of metastases (liver, lung or bone only), duration of treatment with prior CDK4/6 inhibitors (CDK4/6i) in 1L (≥12 or <12 months), comorbid conditions (diabetes, pre-diabetes, or absence of these), ECOG status (0-1 or 2), and presence of biomarkers. Treatment options, based on the mutation profile, included: alpelisib+fulvestrant, capivasertib+fulvestrant, CDK4/6i+fulvestrant, chemotherapy, elacestrant, everolimus + exemestane, or others. In only 4 profiles did most oncologists agree on the 2L treatment; these profiles involved patients with one of the following biomarker alterations: PTEN and PIK3CA (51% agreement), AKT1 and PIK3CA (52% agreement), AKT1 and no ESR1 (57% agreement), and AKT1, PIK3CA, and no ESR1 (50% agreement). In these 4 cases, ≥50% selected capivasertib+fulvestrant, while the second most common treatment selected was alpelisib+fulvestrant or CDK4/6i +fulvestrant. In 8 profiles, oncologists diverged on treatment selection which involved patients with PIK3CA mutations alone or PIK3CA and co-occurring ESR1 mutations. For these patient profiles, oncologists chose various targeted treatment options with no strong consensus. Conclusions: Our survey findings highlight the importance of biomarker testing in treatment decision-making for patients with metastatic HR+/HER2- breast cancer, particularly in choosing 2L treatment. Notably, there is a lack of consensus on treatment selection across biomarkers in determining 2L treatment approaches. This highlights the need for robust evidence to establish best practices and guide clinical decision-making. Citation Format: Leah Park, Komal Jhaveri, Janelle Cambron-Mellott, Nicole Kashine, Emily Mulvihill. Perceptions and behaviors of US oncologists treating HR-positive HER2-negative metastatic breast cancer in second-line [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-01-08.