Haddad, Tufia C

Introduction Women residing in rural areas or belonging to lower socioeconomic status (SES) strata experience disproportionately low rates of breast cancer screening, contributing to delayed diagnoses and poorer prognoses. In addition, their participation in clinical trials remains markedly limited, reducing opportunities to access preventive and screening interventions. Promoting research preparedness among women before disease onset may empower them to make informed decisions regarding their health and willingness to participate in clinical research with fewer emotional and logistical barriers. Methods and analysis This project applies a community-based participatory research approach to develop and refine the WeCARE (Women’s Engagement for Cancer Awareness, Resources and Education) intervention for women aged 50–74 years who have either never undergone breast cancer screening or have not received screening in the past 5 years and who reside in rural areas or belong to low SES groups. The intervention consists of two components. Component 1 is a single-day, in-person community forum that includes (a) an educational seminar led by an oncologist to address breast cancer risk and screening guidelines, (b) survivor storytelling to enhance emotional engagement and cultural resonance and (c) facilitated navigation to breast cancer screening and future research participation. Component 2 involves structured post-forum follow-up through multiple touchpoints (phone calls and mailed boosters) to reinforce knowledge, address barriers and support screening completion and research enrolment. Quantitative data (eg, screening completion, satisfaction and follow-up engagement) will be summarised using descriptive statistics to assess feasibility and reach on 50 participants. Qualitative feedback from participants will undergo thematic analysis to identify barriers, facilitators and perceived cultural relevance. Integrated mixed-method interpretation will inform iterative refinement of the WeCARE intervention and guide design of subsequent larger trials. Ethics and dissemination Approved by the Mayo Clinic Institutional Review Board (IRB #25–008934). All participants will provide informed consent. Procedures ensure confidentiality, cultural sensitivity and participant safety. Data will be stored in REDCap and disseminated through publications, conferences, local town halls and community reports.

PURPOSE Limited access to high-speed internet (broadband [BB]) may pose challenges to video telehealth visit (VTV) utilization. This study explored barriers, facilitators, and attitudes toward VTV adoption in patients with cancer residing in low-BB settings. METHODS We examined a cohort of patients with cancer receiving longitudinal care at Mayo Clinic Cancer Practice in the Upper Midwest. Eligible patients had ≥6 in-person visits during July 2020-October 2022, received oncology care at Mayo Clinic sites, were alive at sampling, and resided in low-BB areas defined by Federal Communications Commission data as 0 or 1 internet service provider offering <25 Mbps. We enrolled 24 participants stratified into two groups: (1) Transitioned users (TUs): adopted VTVs postpandemic (November 2022-December 2023); (2) persistent nonusers (PNUs): received exclusively in-person visits. Semistructured telephone interviews were conducted in June 2024 and thematically analyzed. RESULTS The average age of participants was 71.3 years (range, 42-88), 50% was female, and all identified as White. Three themes emerged: (1) Structural and clinical constraints—physical examinations, laboratory testing, and chemotherapy administration were viewed as requiring in-person care, whereas VTVs were perceived acceptable for routine follow-ups; (2) Skills and experience—digital literacy was generally adequate, but confidence and direct exposure to VTV distinguished TU from PNU; (3) Motivations—both groups preferred in-person care for cancer-related emotional reassurance. TU cited weather, travel burden, and proactive provider offering as adoption triggers, whereas PNU reported that VTV was rarely offered. TU focused on system-level solutions, whereas PNUs preferred individual-level resources. CONCLUSION Differential VTV adoption in low-BB settings reflected exposure, provider offering, and situational necessity rather than BB access alone. Oncology practices should consider normalizing the hybrid care model combining in-person and video appointment visits and provide tailored supports to advance equitable telemedicine. Expanding video care in oncology requires more than digital access and depends on patient experience, care context, and human connection inherent in oncology care.

Abstract Purpose: The neutralizing peptibody trebananib prevents angiopoietin-1 and angiopoietin-2 from binding with Tie2 receptors, inhibiting angiogenesis and proliferation. Trebananib was combined with paclitaxel±trastuzumab in the I-SPY2 breast cancer trial. Patients and Methods: I-SPY2, a phase II neoadjuvant trial, adaptively randomizes patients with high-risk, early-stage breast cancer to one of several experimental therapies or control based on receptor subtypes as defined by hormone receptor (HR) and HER2 status and MammaPrint risk (MP1, MP2). The primary endpoint is pathologic complete response (pCR). A therapy “graduates” if/when it achieves 85% Bayesian probability of success in a phase III trial within a given subtype. Patients received weekly paclitaxel (plus trastuzumab if HER2-positive) without (control) or with weekly intravenous trebananib, followed by doxorubicin/cyclophosphamide and surgery. Pathway-specific biomarkers were assessed for response prediction. Results: There were 134 participants randomized to trebananib and 133 to control. Although trebananib did not graduate in any signature [phase III probabilities: Hazard ratio (HR)-negative (78%), HR-negative/HER2-positive (74%), HR-negative/HER2-negative (77%), and MP2 (79%)], it demonstrated high probability of superior pCR rates over control (92%–99%) among these subtypes. Trebananib improved 3-year event-free survival (HR 0.67), with no significant increase in adverse events. Activation levels of the Tie2 receptor and downstream signaling partners predicted trebananib response in HER2-positive disease; high expression of a CD8 T-cell gene signature predicted response in HR-negative/HER2-negative disease. Conclusions: The angiopoietin (Ang)/Tie2 axis inhibitor trebananib combined with standard neoadjuvant therapy increased estimated pCR rates across HR-negative and MP2 subtypes, with probabilities of superiority &gt;90%. Further study of Ang/Tie2 receptor axis inhibitors in validated, biomarker-predicted sensitive subtypes is warranted.

PURPOSE BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib. METHODS Patients were categorized at baseline according to WHO BMI categories. Neutropenia rates were assessed with univariable and multivariable logistic regression. Time to early discontinuation of palbociclib was analyzed with Fine and Gray competing risk models. Unstratified Cox models were used to investigate the association between BMI category and time to invasive disease-free survival (iDFS). 95% CIs were derived. RESULTS Of 5,698 patients included in this analysis, 68 (1.2%) were underweight, 2,082 (36.5%) normal weight, 1,818 (31.9%) overweight, and 1,730 (30.4%) obese at baseline. In the palbociclib arm, higher BMI was associated with a significant decrease in neutropenia (unadjusted odds ratio for 1-unit change, 0.93; 95% CI, 0.91 to 0.94; adjusted for age, race ethnicity, region, chemotherapy use, and Eastern Cooperative Oncology Group at baseline, 0.93; 95% CI, 0.92 to 0.95). This translated into a significant decrease in treatment discontinuation rate with higher BMI (adjusted hazard ratio [HR] for 10-unit change, 0.75; 95% CI, 0.67 to 0.83). There was no significant improvement in iDFS with the addition of palbociclib to ET in any weight category (normal weight HR, 0.84; 95% CI, 0.63 to 1.12; overweight HR, 1.10; 95% CI, 0.82 to 1.49; and obese HR, 0.95; 95% CI, 0.69 to 1.30) in this analysis early in follow-up (31 months). CONCLUSION This preplanned analysis of the PALLAS trial demonstrates a significant impact of BMI on side effects, dose reductions, early treatment discontinuation, and relative dose intensity. Additional long-term follow-up will further evaluate whether BMI ultimately affects outcome.

PURPOSE In response to the COVID-19 pandemic, many cancer practices rapidly adopted telehealth services. However, there is a paucity of data regarding ongoing telehealth visit utilization beyond this initial response. The purpose of this study was to assess changes in variables associated with telehealth visit utilization over time. METHODS This is a cross-sectional, year-over-year, retrospective analysis of telehealth visits conducted across a multisite, multiregional cancer practice in the United States. Multivariable models examined the association of patient- and provider-level variables with telehealth utilization across outpatient visits conducted over three 8-week periods from July to August in 2019 (n = 32,537), 2020 (n = 33,399), and 2021 (n = 35,820). RESULTS The rate of telehealth utilization increased from <0.01% (2019) to 11% (2020) to 14% (2021). The most significant patient-level factors associated with increased telehealth utilization included nonrural residence and age ≤65 years. Among patients residing in rural settings, video visit utilization rates were significantly lower and phone visit utilization rates were significantly higher compared with patients from nonrural residences. Regarding provider-level factors, widening differences in telehealth utilization were observed at tertiary versus community-based practice settings. Increased telehealth utilization was not associated with duplicative care as per-patient and per-physician visit volumes in 2021 remained consistent with prepandemic levels. CONCLUSION We observed continuous expansion in telehealth visit utilization from 2020 to 2021. Our experiences suggest that telehealth can be integrated into cancer practices without evidence of duplicative care. Future work should examine sustainable reimbursement structures and policies to ensure accessibility of telehealth as a means to facilitate equitable, patient-centered cancer care.

PURPOSE The PALLAS study investigated whether the addition of palbociclib, an oral CDK4/6 inhibitor, to adjuvant endocrine therapy (ET) improves invasive disease-free survival (iDFS) in early hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) breast cancer. In this analysis, we evaluated palbociclib exposure and discontinuation in PALLAS. METHODS Patients with stage II-III HR+, HER2– disease were randomly assigned to 2 years of palbociclib with adjuvant ET versus ET alone. The primary objective was to compare iDFS between arms. Continuous monitoring of toxicity, dose modifications, and early discontinuation was performed. Association of baseline covariates with time to palbociclib reduction and discontinuation was analyzed with multivariable competing risk models. Landmark and inverse probability weighted per-protocol analyses were performed to assess the impact of drug persistence and exposure on iDFS. RESULTS Of the 5,743 patient analysis population (2,840 initiating palbociclib), 1,199 (42.2%) stopped palbociclib before 2 years, the majority (772, 27.2%) for adverse effects, most commonly neutropenia and fatigue. Discontinuation of ET did not differ between arms. Discontinuations for non–protocol-defined reasons were greater in the first 3 months of palbociclib, and in the first calendar year of accrual, and declined over time. No significant relationship was seen between longer palbociclib duration or ≥ 70% exposure intensity and improved iDFS. In the weighted per-protocol analysis, no improvement in iDFS was observed in patients receiving palbociclib versus not (hazard ratio 0.89; 95% CI, 0.72 to 1.11). CONCLUSION Despite observed rates of discontinuation in PALLAS, analyses suggest that the lack of significant iDFS difference between arms was not directly related to inadequate palbociclib exposure. However, the discontinuation rate illustrates the challenge of introducing novel adjuvant treatments, and the need for interventions to improve persistence with oral cancer therapies.

PURPOSE Palbociclib is a cyclin-dependent kinase 4 and 6 inhibitor approved for advanced breast cancer. In the adjuvant setting, the potential value of adding palbociclib to endocrine therapy for hormone receptor–positive breast cancer has not been confirmed. PATIENTS AND METHODS In the prospective, randomized, phase III PALLAS trial, patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative early breast cancer were randomly assigned to receive 2 years of palbociclib (125 mg orally once daily, days 1-21 of a 28-day cycle) with adjuvant endocrine therapy or adjuvant endocrine therapy alone (for at least 5 years). The primary end point of the study was invasive disease-free survival (iDFS); secondary end points were invasive breast cancer–free survival, distant recurrence-free survival, locoregional cancer-free survival, and overall survival. RESULTS Among 5,796 patients enrolled at 406 centers in 21 countries worldwide over 3 years, 5,761 were included in the intention-to-treat population. At the final protocol-defined analysis, at a median follow-up of 31 months, iDFS events occurred in 253 of 2,884 (8.8%) patients who received palbociclib plus endocrine therapy and in 263 of 2,877 (9.1%) patients who received endocrine therapy alone, with similar results between the two treatment groups (iDFS at 4 years: 84.2% v 84.5%; hazard ratio, 0.96; CI, 0.81 to 1.14; P = .65). No significant differences were observed for secondary time-to-event end points, and subgroup analyses did not show any differences by subgroup. There were no new safety signals for palbociclib in this trial. CONCLUSION At this final analysis of the PALLAS trial, the addition of adjuvant palbociclib to standard endocrine therapy did not improve outcomes over endocrine therapy alone in patients with early hormone receptor–positive breast cancer.

PURPOSE: The goal of this study was to assess the impact of an interdisciplinary remote patient monitoring (RPM) program on clinical outcomes and acute care utilization in cancer patients with COVID-19. METHODS: This is a cross-sectional analysis following a prospective observational study performed at Mayo Clinic Cancer Center. Adult patients receiving cancer-directed therapy or in recent remission on active surveillance with polymerase chain reaction–confirmed SARS-CoV-2 infection between March 18 and July 31, 2020, were included. RPM was composed of in-home technology to assess symptoms and physiologic data with centralized nursing and physician oversight. RESULTS: During the study timeframe, 224 patients with cancer were diagnosed with COVID-19. Of the 187 patients (83%) initially managed in the outpatient setting, those who did not receive RPM were significantly more likely to experience hospitalization than those receiving RPM. Following balancing of patient characteristics by inverse propensity score weighting, rates of hospitalization for RPM and non-RPM patients were 2.8% and 13%, respectively, implying that the use of RPM was associated with a 78% relative risk reduction in hospital admission rate (95% CI, 54 to 102; P = .002). Furthermore, when hospitalized, these patients experienced a shorter length of stay and fewer prolonged hospitalizations, intensive care unit admissions, and deaths, although these trends did not reach statistical significance. CONCLUSION: The use of RPM and a centralized virtual care team was associated with a reduction in hospital admission rate and lower overall acute care resource utilization among cancer patients with COVID-19.

Abstract Purpose: This open-label, multicenter, phase IB/II study evaluated sapanisertib, a dual inhibitor of mTOR kinase complexes 1/2, plus exemestane or fulvestrant in postmenopausal women with hormone receptor–positive (HR+)/HER2-negative (HER2−) advanced/metastatic breast cancer. Patients and Methods: Eligible patients had previously progressed on everolimus with exemestane/fulvestrant and received ≤3 (phase IB) or ≤1 (phase II) prior chemotherapy regimens. Patients received sapanisertib 3 to 5 mg every day (phase IB), or 4 mg every day (phase II) with exemestane 25 mg every day or fulvestrant 500 mg monthly in 28-day cycles. Phase II enrolled parallel cohorts based on prior response to everolimus. The primary objective of phase II was to evaluate antitumor activity by clinical benefit rate at 16 weeks (CBR-16). Results: Overall, 118 patients enrolled in phase IB (n = 24) and II (n = 94). Five patients in phase IB experienced dose-limiting toxicities, at sapanisertib doses of 5 mg every day (n = 4) and 4 mg every day (n = 1); sapanisertib 4 mg every day was the MTD in combination with exemestane or fulvestrant. In phase II, in everolimus-sensitive versus everolimus-resistant cohorts, CBR-16 was 45% versus 23%, and overall response rate was 8% versus 2%, respectively. The most common adverse events were nausea (52%), fatigue (47%), diarrhea (37%), and hyperglycemia (33%); rash occurred in 17% of patients. Molecular analysis suggested positive association between AKT1 mutation status and best treatment response (complete + partial response; P = 0.0262). Conclusions: Sapanisertib plus exemestane or fulvestrant was well tolerated and exhibited clinical benefit in postmenopausal women with pretreated everolimus-sensitive or everolimus-resistant breast cancer.