New England Cancer Specialists

Abstract Introduction: Abemaciclib, a CDK4/6 inhibitor, reduces the risk of recurrence in patients (pts) with high-risk HR+/HER2- early breast cancer; use is associated with toxicities, particularly diarrhea, which can impact pts’ ability to maintain dose and/or remain on therapy. TRADE (NCT06001762) is a phase 2, investigator-initiated single-arm trial designed to evaluate whether an initial dose-escalation strategy improves adjuvant abemaciclib tolerability. The study met its primary endpoint, showing the dose escalation strategy reduced treatment discontinuation and improved ability to reach/maintain the target dose of 150 mg BID at 12 weeks (wks), compared to historical controls. Here, we present 6-month follow-up results from TRADE. Methods: Pts with HR+/HER2- early breast cancer eligible for abemaciclib with adjuvant endocrine therapy were enrolled. All pts initiated abemaciclib at 50 mg BID for 2 wks, escalated to 100 mg BID for 2 wks, and then to 150 mg BID onward for a planned 2-year course. Dose escalation required the absence of ongoing grade 3/4 or persistent grade 2 adverse events (AEs). Management of AEs and dose reductions beyond 12 wks was per standard of care. Data on adherence to oral therapy and ctDNA dynamics were collected. Results: Ninety pts were enrolled; median age was 58 years (range 24-78), and the majority were White (80.0%). 51.1% had stage II disease and 48.9% stage III disease. 73.3% had received chemotherapy in the neo/adjuvant setting. All pts received an adjuvant aromatase inhibitor (AI), 17.8% with ovarian function suppression. One pt had progression within 24 wks of treatment, hence was excluded from dose-related analyses. Out of 89 evaluable pts, 72 (80.9%) remained on treatment at 24 wks; 46 (63.9%) were receiving abemaciclib at 150 mg BID, 18 (25.0%) at 100 mg BID and 8 (11.1%) at 50 mg BID. Abemaciclib discontinuation occurred in 6 pts (6.7%) during the first 12 wks and in an additional 11 pts (12.4%) between wks 12 and 24, resulting in a cumulative discontinuation rate of 19.1% (n=17) over the initial 24 wks of exposure. The most common reasons for discontinuation were AEs (7, 7.9%) and withdrawal of consent/patient preference (6, 6.7%). Specific AEs contributing to discontinuation included diarrhea (2, 2.2%), pneumonitis (2, 2.2%), transaminitis (1, 1.1%), allergic reaction (1, 1.1%), and other (1, 1.1%). Of those who discontinued for patient preference, 5 of the 6 had reached target dose, of whom 3 did not have a dose reduction. A total of 12 pts (13.5%) did not reach target dose, and 29 (32.6%) required dose reductions within 24 wks, primarily due to gastrointestinal or hematologic toxicities, 22 (24.7%) with reductions from 150 mg dosing. The most frequently reported AEs overall were diarrhea (grade ≥2 32.2%, grade 3 5.6%), neutropenia (31.1%, grade ≥3 4.4%), and fatigue (25.6%, no grade ≥3). When analyzed by 4-wk intervals, rates of grade >2 diarrhea were 8.9% (wks 1-4), 19.1% (wks 5-8), 16.5% (wks 9-12), 12.0% (wks 13-16), 8.9% (wks 17-20), and 9.5% (wks 21-24), showing an early peak and gradual decline over time. Patient-reported outcomes, measured by FACT-B assessments, indicated that quality of life remained stable throughout the study period. Additional analyses, including evaluation of adherence and ctDNA, are ongoing. Conclusions: In the TRADE study, after initial dose escalation, abemaciclib was generally well tolerated, with a cumulative discontinuation rate of 19.1% at 24 wks, 7.9% for AE. The incidence of grade >2 diarrhea peaked at month 2 and declined over time. The majority of pts maintained quality of life and were able to remain on therapy with manageable and expected toxicities. These updated findings continue to support the feasibility of an initial abemaciclib dose-escalation approach to optimize drug exposure and reduce early discontinuation, while preserving therapeutic intensity. Citation Format: I. Schlam, D. Trapani, S. Kim, M. Faggen, N. Sinclair, P. Sanz-Altamira, C. Battelli, S. Berwick, S. Lo, J. Acevedo, S. Sinclair, A. Malcom, L. Varella, S. L. Sammons, S. T. Schumer, P. D. Poorvu, E. P. Wallace, E. Pasternak, N. Tayob, S. M. Tolaney, E. L. Mayer. Trade: 6-month abemaciclib tolerability after initial dose escalation in early HR+/HER2- breast cancer [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 PD1-08.

The likelihood of finding a human leukocyte antigen (HLA)-matched unrelated donor (MUD) for hematopoietic cell transplantation can be predicted using a donor search prognosis score. Patients without a MUD may use alternative donors (haploidentical related, mismatched unrelated, or umbilical cord blood). This multicenter biological assignment trial was conducted by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1702). Eligibility criteria were broad to mirror clinical practice. The primary end point was 2-year survival from evaluability and compared between those Very Likely (>90%) and Very Unlikely (<10%) to find a MUD. All other patients, Less Likely to find a MUD, were enrolled in an observational arm. Transplant outcomes were compared for all three groups. A total of 1,751 evaluable patients at 47 centers were Very Likely (54.7%), Less Likely (29.5%), and Very Unlikely (15.8%) to identify a MUD. Survival did not differ in univariate (hazard ratio [HR], 1.00 [95% CI, 0.82 to 1.21]; P = .98) or multivariate (HR, 1.07 [95% CI, 0.86 to 1.33]; P = .56) analyses between the Very Unlikely and Very Likely groups, measured through 2 years from the beginning of a search for a MUD or alternative donor. Of the transplanted patients (n = 1,179), MUD was used for 94% of the Very Likely, 38% of Less Likely, and 9% of Very Unlikely patients. Multivariate analyses showed no differences in relapse, treatment-related mortality, disease-free survival, and acute and chronic graft-versus-host diseases for the three search prognosis groups after transplantation. Using a donor search prognosis strategy to prioritize an alternative donor for patients Very Unlikely to find a MUD resulted in survival and transplant outcomes that were not statistically different compared with those Very Likely to find a MUD.