182 Background: BsAbs are a newer form of cancer immunotherapy with multiple approved agents in the US. Key barriers to use of BsAbs include the risk of adverse events (AEs): cytokine release syndrome (CRS) and immune effect-cell associated neurotoxicity syndrome (ICANS) requiring inpatient administration during ramp-up dosing. These clinical and logistic factors can limit access, and delay utilization of BsAbs in the community oncology (CO) setting. We present results of out-pt BsAb ramp-up from a single, medium-sized, CO practice. Methods: We created a fully out-pt, BsAb multidisciplinary (multiD) program with guidance and accreditation from national experts in the Exigent Network. A dedicated BsAb team of physicians, advanced practice providers, pharmacists, and nurses was established with a distinct BsAb on-call roster, and access to clinic, infusion center and tocilizumab (toci) on a 24-hour basis. Eligible patients (pts) had to reside within 1 hour of clinic, PS 0-2, no active brain metastases, a reliable caregiver, consistent access via phone, reliable transportation, and willing to learn and report vitals and status updates via telehealth consistently during ramp-up dosing. Education was provided to ER staff and ICU staff at a partner community hospital regarding BsAb AE identification and management. Results: From June 2024-May 2026 total of 44 ramp up cycles were completed (for 40 unique pts), with 7 BsAb products (Table) in 19 females, 21 males; median age 68 (range 50-89) years; PS1 (34) and PS2 (6). Of the 44 ramp-up cycles, 14 (32%) episodes of CRS were noted: Grade 1 (11) and grade 2 (3). Acute events occurred in 4 pts, including 2 deaths- all in tarlatamab treated patients: One pt had hypertension, managed in the ER; 2 nd pt with fever and neutropenia concurrent grade 2 CRS (recovered). Two deaths occurred- one patient had rising bilirubin with liver metastases and PS 2 prior to BsAb initiation- admitted with sepsis and opted for withdrawal of care. A second pt reported to ER after tarlatamab for pneumonia and discontinued all treatment opting for comfort measures. None were deemed secondary to BsAb associated AEs. Six patients were treated with toci for CRS during ramp–up (5 of 6 after-hours). Prophylactic toci was used in 5 pts for talquetamab/teclistamab after May 2025. Conclusions: A standardized protocol for patient assessment, monitoring, and toxicity management with a multi-D BsAb program facilitated the safe delivery of BsAb therapy in the community setting. These data suggest that protocol-driven care may reduce perceived barriers to treatment and increase access for patients who may otherwise be considered ineligible or lack access. BsAbs administered. Tarlatamab 19 Epcortimab 9 Mosunetuzumab 4 Talquetamab 4 Glofitamab 3 Teclistamab 3 Tebentafusp 2 Total ramp up cycles 44
OBJECTIVE:To describe real-world care models for teclistamab step-up dosing (SUD) and considerations for successful implementation among community-based practices and/or practices employing outpatient SUD. METHODS:This mixed-methods study involved a survey, interviews, and roundtable discussion with US providers with real-world teclistamab experience. Survey topics included their practice's SUD model, adverse event management, and transition of care processes. Select survey respondents were interviewed to describe their practices' SUD models in-depth and barriers/facilitators to these models. A subsequent roundtable was held to provide additional context on current models. RESULTS:A total of 38 clinicians from unique practices completed the survey between March-August 2024; 76% worked at community-based practices and 66% had treated ≥5 multiple myeloma patients with teclistamab. Among survey participants, eight completed an interview and seven joined the roundtable. Among the 38 practices, 53% employed outpatient SUD, 26% inpatient SUD, and 21% referred out for SUD. Patient-level requirements for outpatient SUD (n = 20) included caregiver support (90%), proximity to administering site (70%), good performance status (65%), and low disease burden (30%). The top factors which triggered inpatient admissions were any grade immune effector cell-associated neurotoxicity syndrome (85%), grade ≥2 cytokine release syndrome (70%), and abnormal vital signs (60%). Over a quarter of practices (29%) used tocilizumab prophylactically. CONCLUSION:Outpatient teclistamab SUD has been successfully implemented in real-world practice for appropriately selected patients. This study provides insights into real-world outpatient SUD, including in community practices, to inform providers seeking to implement similar models to improve patient access while reducing cost and resource burden.
PURPOSE:In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy. METHODS:In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS). SET2,3 was tested on the 682 banked RNA samples from ER+ cancers. RESULTS:Dose-dense chemotherapy improved DFS in the overall study population by 23% (HR, 0.77 [95% CI, 0.66 to 0.90]) and OS by 20% (HR, 0.80 [95% CI, 0.67 to 0.95]); the benefits of dose-dense therapy were seen for ER+ and ER-negative subsets, without significant interaction between treatment arm and ER status. Low SET2,3 status was highly prognostic, but also predicted improved outcomes from dose-dense chemotherapy (interaction P = .0998 for DFS; 0.027 for OS), independent of menopausal status. Specifically, low endocrine transcriptional activity predicted benefit from dose-dense chemotherapy, whereas tumor burden and proliferation-driven signatures for molecular subtype classification did not. CONCLUSION:At 12-year follow-up, C9741 confirmed the sustained long-term benefit of adjuvant dose-dense chemotherapy for node-positive breast cancer. SET2,3 identified patients with ER+ breast cancer who benefited from dose-dense chemotherapy, and specifically, this benefit was predicted by low endocrine activity in the cancer, rather than tumor burden, molecular subtype, or menopausal status.
One barrier to participating in clinical research is that patients with low literacy skills (1 in 5 US adults) may struggle to understand the informed consent document (ICD). Writing consents using health literacy and plain language guidelines including simplified syntax and semantics can increase understandability and facilitate inclusivity of research populations with literacy challenges. Our study aim was to evaluate a simplified ICD for understandability while considering factors known to relate to comprehension (reading skills and working memory). We performed an on-line survey of 192 adults ages 18-77 in Georgia. Participants performed significantly better on the simplified ICD test. We built an additional model with all version x measure interactions (i.e., age, sex, race, urbanicity, GMVT, WM). This model did not significantly improve model fit, F < 1.00, suggesting that individual differences did not moderate the effect of simplification. Our findings suggest that using plain language and simplified syntax and semantics in ICD as a universal precaution may reduce cognitive reading burden for adults regardless of differences in reading skill or working memory. Increasing understandability in ICD may help improve targets for clinical trial enrollment.
Purpose To update evidence-based guideline recommendations for practicing oncologists and others on systemic therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer to 2018. Methods An Expert Panel conducted a targeted systematic literature review (for both systemic treatment and CNS metastases) and identified 622 articles. Outcomes of interest included overall survival, progression-free survival, and adverse events. Results Of the 622 publications identified and reviewed, no additional evidence was identified that would warrant a change to the 2014 recommendations. Recommendations HER2-targeted therapy is recommended for patients with HER2-positive advanced breast cancer, except for those with clinical congestive heart failure or significantly compromised left ventricular ejection fraction, who should be evaluated on a case-by-case basis. Trastuzumab, pertuzumab, and taxane for first-line treatment and trastuzumab emtansine for second-line treatment are recommended. In the third-line setting, clinicians should offer other HER2-targeted therapy combinations or trastuzumab emtansine (if not previously administered) and may offer pertuzumab if the patient has not previously received it. Optimal duration of chemotherapy is at least 4 to 6 months or until maximum response, depending on toxicity and in the absence of progression. HER2-targeted therapy can continue until time of progression or unacceptable toxicities. For patients with HER2-positive and estrogen receptor-positive/progesterone receptor-positive breast cancer, clinicians may recommend either standard first-line therapy or, for selected patients, endocrine therapy plus HER2-targeted therapy or endocrine therapy alone. Additional information is available at www.asco.org/breast-cancer-guidelines .
