8504 Background: Pralsetinib, an oral tyrosine kinase inhibitor, selectively and potently targets oncogenic RET fusion and mutation proteins. Pralsetinib is FDA approved to treat adults with metastatic RET -altered NSCLC. We present efficacy and safety of pralsetinib vs standard of care (SOC) in first-line RET fusion-positive NSCLC from a randomized phase 3, open-label study, AcceleRET-Lung (NCT04222972). Methods: AcceleRET-Lung was conducted at 74 sites in 22 countries. Adults with RET fusion-positive advanced or metastatic NSCLC received pralsetinib 400 mg/d or platinum-based SOC therapy. Crossover to pralsetinib was optional upon progression. The primary end point was progression-free survival (PFS) per RECIST v1.1. Secondary end points included overall response rate (ORR), overall survival (OS), duration of response (DOR), and safety. Efficacy was evaluated in randomized patients (intent-to-treat population [ITT]). Safety was assessed in patients receiving ≥1 dose of study drug. Results: 223 ITT patients were randomized to pralsetinib (n=110) or SOC (n=113). Pralsetinib and SOC groups had similar baseline characteristics (median age: 62 and 63 y, respectively; female: 48% and 57%; median lesions: both 4; brain metastases: 15% and 16%). The study was terminated early per sponsor decision on January 27, 2025. ITT patients in the pralsetinib group had significantly greater median PFS vs SOC (18.7 vs 9.0 mo; P =0.003), ORR (65.5% vs 41.6%; P <0.001), and median DOR (20.6 vs 9.7 mo; P =0.004; Table). Safety was generally consistent with the known pralsetinib profile except for a higher rate of infection in the pralsetinib group vs SOC (71.3% vs 51.9%), including pneumonia (19.4% vs 5.8%), urinary tract infections (17.6% vs 7.7%), and opportunistic infections (9.3% vs 1.0%). There were 32 (30.0%) and 26 (25.0%) deaths in the pralsetinib and SOC groups, respectively, with 8 (7.4%) and 0 due to infection. Common grade ≥3 TRAEs in the pralsetinib vs SOC groups were hypertension (11.1% vs 0), neutropenia (10.2% vs 8.7%), anemia (8.3% vs 10.6%), and decreased neutrophil count (7.4% vs 4.8%). Conclusions: In a Phase 3 study, pralsetinib met the primary PFS end point and had a significantly greater and more durable ORR vs SOC, confirming the clinical utility of pralsetinib in RET fusion-positive NSCLC. Monitoring for infections with pralsetinib is warranted. Clinical trial information: (1) NCT04222972 ; (2) 2023-505035-12-00; (3) 2019-002463-10. Efficacy outcomes. Pralsetinib (n=110) SOC(n=113) Stratified hazard ratio/odds ratio (95% CI) P Value Duration of follow-up, mo, median (range) 20.5(0, 49.8) 16.0(0, 42.3) - - PFS, mo, median (95% CI) 18.7(11.1, 25.2) 9.0(7.1, 11.5) 0.59(0.42, 0.84) 0.003 ORR, % (95% CI) 65.5(55.8, 74.3) 41.6(32.4, 51.2) 2.81(1.61, 4.93) <0.001 OS, mo, median (95% CI) NR (29.6, NR) 39.8(39.8, NR) 1.09(0.65, 1.85) 0.742 DOR, mo, median (95% CI) 20.6(17.2, 31.8) 9.7(7.6, 15.9) 0.48(0.28, 0.80) 0.004
Breast cancer (BC) treatment is increasingly complex, with a strong need for coordinated decision-making among specialists within multidisciplinary teams (MDTs). Despite their critical role in optimizing patient care, limited data exist on the structure and functioning of BC MDTs in Portugal. To address this gap, the PRISMA study collected both qualitative and quantitative data to characterize the organization, composition, and operational practices of BC MDT meetings across various regions and healthcare sectors nationwide. A mixed-methods approach was used to analyze multidisciplinary team practices from January 2022 to June 2023. For qualitative data, a Delphi methodology was applied through a questionnaire developed from a systematic literature review. Sixty-four Portuguese specialists involved in BC MDT meetings during this period were invited to participate. Two rounds of anonymous online voting were conducted from October 2024 to December 2024, using a five-point Linkert scale; consensus was defined as ≥ 80% concordance among responses. For the quantitative data, retrospective aggregated information from MDT meetings were collected. Forty-six specialists from 13 Portuguese centers participated in the Delphi panel, including representatives from 3 cancer institutes, 3 university hospitals, and 9 general hospitals, encompassing the private (3 centers) and public (10 centers) healthcare sectors. Ten centers also participated in the quantitative phase of the study, where MDT meetings have been held for an average of 18 years. During the study period, each center held an average of 88 meetings, with each meeting lasting approximately 2.3 hours. Most teams had 5-10 members (70%), including medical oncologists (100%), breast surgeons (100%), radiologists (90%), radiation oncologists (90%), pathologists (70%), and oncology nurses (60%). Additional medical and other specialties represented in at least one center included gynecology, nuclear medicine, social service, geriatrics, and data managers. These findings were validated by the Delphi panel, which underscored the role of specialized MDTs with core and supplementary members. During the study period, most meetings were conducted in a hybrid format (60%), with presential (40%) and virtual (30%) formats also reported. On average, 15 cases were discussed per meeting, totaling approximately 767 annually. Of these, on average 45 cases were revised, mainly due to missing prior information (70%). Experts participating in the Delphi panel considered MDT meetings crucial for delivering evidence-based, personalized treatment and minimizing patient care disparities. Key challenges identified included time constraints, delays in diagnosis and staging procedures, and staff shortages. MDT meetings are well established in Portuguese centers and align with international recommendations. This study, through a mixed-methods approach, identified both strengths and operational challenges in MDT practices. Experts emphasize their critical role in ensuring evidence-based, patient-centered care. Findings support efforts to standardize and strengthen MDT functioning to ensure high-quality breast cancer care nationwide. G. Sousa, A. M. Ferreira, I. Pereira, C. Abreu, D. Simão, F. Machado, G. Fernandes, R. A. Leonor, J. Fougo, M. C. Nogueira, P. H. Meireles, J. Abreu Sousa, P. F. Cortes. Multidisciplinary Team Decision-Making in Breast Cancer: Real-World Insights from the PRISMA Study [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 PS5-11-05.
Breast cancer (BC) is the most common cancer and the leading cause of cancer-related death in women. Triple-negative BC (TNBC) and high-risk ER+ HER2- BC are aggressive BC subtypes with high recurrence rates. In Portugal, data on treatment of TNBC and high-risk ER+HER2- BC is limited. To address this, the PRISMA study collected quantitative data on treatment patterns and pathological complete response (pCR) from multiple Portuguese centers. Retrospective aggregated data from patients diagnosed between Jan-2019 and Jun-2023 were collected. The study included adult patients diagnosed with stage II - III TNBC or high-risk ER+ HER2- BC eligible for neoadjuvant (NAT) chemotherapy. The study included 1585 patients, 642 (40%) with TNBC and 943 (60 %) with high-risk ER+HER2- BC. Most patients were ≥65 years with 1% being male. In both cohorts, most were diagnosed with stage II and were postmenopausal (62% and 73% in TNBC; 42% and 53% in ER+HER2-, respectively). Carcinoma of no special type was the predominant histology (88% TNBC and 83% ER+HER2- BC). In TNBC patients, the mean time between therapeutic decision and treatment initiation was five weeks (1 to 29 weeks), and from NAT completion to surgery was six weeks (3 to 8 weeks). Most TNBC patients underwent NAT chemotherapy (93%), primarily with carboplatin/paclitaxel and cyclophosphamide/doxorubicin or epirubicin (48%), resulting in a pCR rate of 47%. Surgery was performed in 99% of patients, with 59% undergoing conservative surgery. Adjuvant (AT) chemotherapy was given to 31% of patients, mostly with capecitabine (77%). Radiotherapy (RT) was performed in 72% of patients, primarily (66%) after conservative surgery, using conventional fractionation (50Gy/25fr, 48%). Among high-risk ER+HER2- BC patients, 81% cancers had Ki-67 ≥20%, and multi-gene assays were performed in 6%. 82% of high-risk ER+/HER2- patients underwent NAT and achieved a pCR of 9%. Dose dense AC or EC plus weekly paclitaxel was the most commonly used regimen (51%). The mean interval between NAT completion and surgery was 8 weeks (3 to 23 weeks). 59% of 939 patients undergoing surgery underwent breast conserving surgery. AT chemotherapy was administered to 18%, mostly with dose dense AC or EC and paclitaxel weekly (28%). RT was performed in 90% of patients, and 55% receiving it after conservative surgery. Regarding endocrine therapy (ET), 85% underwent adjuvant ET, with 68% using aromatase inhibitors. Ovarian suppression was performed in 26% of patients, frequently using gonadotropin-releasing hormone inhibitors (87%). The data provides a real-world characterization of TNBC and high-risk ER+HER2- BC treatment, demonstrating a high adherence to NAT chemotherapy and adjuvant ET, per guidelines, in this period. Observed delays in surgery suggest inter-hospital care variations that may inform healthcare policy, ultimately improving patient outcomes. G. Sousa, A. M. Ferreira, I. Pereira, A. Catarina, D. Simão, F. Machado, G. Fernandes, L. A. Ribeiro, J. Fougo, M. C. Nogueira, P. H. Meireles, J. Abreu Sousa, P. Cortes. Real-world evaluation of treatment trends in breast cancer: the PRISMA study [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 PS5-05-11.
