Biomedical subjects

Adam M Brufsky

Publications and source records attributed to Adam M Brufsky.

2 recordsLinked to original sources

PubMed2026

Patient-reported outcomes from the TBCRC 022 study of neratinib and ado-trastuzumab emtansine for HER2-positive breast cancer brain metastases.

PURPOSE: In TBCRC 022 (NCT01494662), neratinib and ado-trastuzumab emtansine (T-DM1) demonstrated intracranial activity among patients with HER2-positive breast cancer brain metastases. However, gastrointestinal (GI) toxicities-particularly diarrhea-were common, potentially impacting quality of life. Clinician-reported adverse event (CTCAE) grading may underestimate the patient experience. We report GI toxicities using patient-reported outcomes (PROs) in TBCRC's neratinib-T-DM1 cohort. METHODS: Patients received neratinib (160 mg daily) and T-DM1 (3.6 mg/kg IV every 21 days). A pre-planned analysis assessed patient-reported GI toxicities during Cycles 1-4 using the Patient-reported Outcomes Measurement Information System (PROMIS) GI Diarrhea scale, Systemic Therapy-Induced Diarrhea Assessment Tool (STIDAT), and PRO-CTCAE. Descriptive statistics and linear mixed effects models evaluated symptom trajectories over time. We evaluated agreement for PRO and clinician-reported data. RESULTS: Forty-four patients enrolled; all completed ≥1 PRO. GI symptom burden increased over Cycles 1-3. PROMIS scores worsened significantly by Cycle 2, with a peak mean increase of 6.62 (95% confidence interval (CI): 2.67-10.59; p = 0.002) at Cycle 3. STIDAT scores also worsened by Cycle 3 (mean change 0.50; 95%CI: 0.11-0.90; p = 0.015). Based on maximum PRO-CTCAE scores, moderate-to-severe symptoms were reported by 20.5% (diarrhea), 24.4% (appetite loss), and 41.0% (constipation). Agreement between PRO-CTCAE and clinician-reported CTCAE was low (kappa <0.2) with clinicians reporting less toxicity. PROMIS and STIDAT scores were significantly correlated. CONCLUSION: This GI-focused PRO analysis highlights the value of PROs in capturing patient-experienced toxicities that impact quality of life yet are underestimated by clinicians. Incorporating PROs into clinical trials can inform supportive care and prophylactic strategies.

Humans↗

PubMed2025

MammaPrint predicts chemotherapy benefit in HR+HER2- early breast cancer: FLEX Registry real-world data.

BACKGROUND: Gene expression assays help personalize adjuvant chemotherapy decisions for hormone receptor-positive, HER2-negative (HR+HER2-) early breast cancer (EBC). The 70-gene risk of distant-recurrence signature, MammaPrint, demonstrated clinical utility in guiding chemotherapy de-escalation in genomically low risk patients in the MINDACT trial. This study evaluates MammaPrint as a continuous predictor of chemotherapy benefit in HR+HER2- EBC using real-world data (RWD) from the FLEX Registry. METHODS: The study evaluated 1002 patients treated with endocrine therapy (ET) only or ET with chemotherapy (ET+CT) enrolled in FLEX (NCT03053193) with 5-year median follow-up. Propensity-score matching balanced treatment groups by menopausal status, T-stage, and nodal status. The primary endpoint was distant recurrence-free interval (DRFI). Regression and Cox proportional hazards models assessed chemotherapy benefit across MammaPrint Index (MPI) risk. RESULTS: Most patients were postmenopausal (70.1%), node-negative (70.0%), and had grade 2 tumors (51.2%). The regression models showed that MPI strongly predicted 5-year DRFI in ET only (R2 = 0.99, P < .001) and ET + CT (R2 = 0.90, P < .001) groups, corresponding to an average absolute chemotherapy benefit of 5.6% in High 1 and 10.9% in High 2. Minimal improvement in DRFI with chemotherapy was observed for Low (1.7%) and UltraLow (<1.0%) risk groups. A multivariate Cox model with an MPI-by-treatment interaction term demonstrated that increasing MPI risk was associated with greater chemotherapy benefit on DRFI (HR = 0.15, P = .047). Chemotherapy benefit was significantly associated with premenopausal status, but not age, T-stage, nodal status, or grade. CONCLUSIONS: These RWD from the FLEX Registry demonstrate that MPI is predictive of both DRFI prognosis and chemotherapy benefit in HR+HER2- EBC. (NCT03053193).

Adult↗