Biomedical subjects

B Pistilli

Publications and source records attributed to B Pistilli.

3 recordsLinked to original sources

PubMed2026

Outcomes of elacestrant in patients with ER-positive, HER2-negative, ESR1-mutated metastatic breast cancer who received prior endocrine therapy and cyclin-dependent kinase inhibitor in a real-world setting.

BACKGROUND: Real-world data analyses show durable benefits with elacestrant, with or without prior treatment with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i). This cohort focused on patients with ER-positive/HER2-negative estrogen receptor 1 (ESR1)-mutated metastatic breast cancer (mBC) treated with elacestrant after at least one line of endocrine therapy (ET) combined with CDK4/6i (N = 281). PATIENTS AND METHODS: Claims data from the Komodo Research Dataset linked with Foundation Medicine clinical-genomics data were used. Primary outcome was median time-to-next-treatment (mTTNT). RESULTS: In patients with ER-positive/HER2-negative ESR1-mutated mBC who received one to two prior lines of ET + CDK4/6i (n = 108), mTTNT with elacestrant was 8.2 months [95% confidence interval (CI) 6.0-12.2]. In patients who received one to two prior lines of ET + CDK4/6i for ≥12 months (n = 85), mTTNT was 9.0 months (95% CI 7.7-13.7), including an mTTNT of 12.2 months (95% CI 9.0-not reached) in those who received one prior line of ET (n = 31). In patients with liver and/or lung metastasis (n = 169), mTTNT was 6.9 months (95% CI 5.8-8.3), whereas it was 7.4 months (95% CI 5.6-12.9) in patients with brain metastasis (n = 68). In patients with coexisting ESR1- and phosphoinositide 3-kinase-pathway-mutated tumors (n = 115), mTTNT was 6.1 months (95% CI 5.0-8.1). CONCLUSIONS: Elacestrant showed durable benefits in patients with ER-positive/HER2-negative ESR1-mutated mBC previously exposed to at least one line of ET + CDK4/6i, reinforcing the role of elacestrant as a potential first-choice option for patients with endocrine-sensitive tumors.

ESR1 mutation↗

PubMed2026

Antibody-drug conjugates in selected solid tumours: a position statement update based on findings from the third workshop held by the ETOP IBCSG Partners Foundation.

The European Thoracic Oncology Platform (ETOP) International Breast Cancer Study Group (IBCSG) Partners Foundation initiated a series of workshops for experts to review current evidence and offer recommendations to guide future antibody-drug conjugate (ADC) research. Here, we summarise key findings from the third workshop, which included experts in various solid tumours, basic/translational research scientists and pharmaceutical industry representatives. Recent positive phase III trial data have further incorporated ADCs into the standard of care [e.g. lung: sacituzumab tirumotecan; breast: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan, datopotamab deruxtecan; muscle-invasive bladder cancer: enfortumab vedotin; ovarian cancer: mirvetuximab soravastine; cervical cancer: tisotumab vedotin]. Thus, research priorities must be tailored according to tumour type, potentially focussing initially on settings where ADCs could replace chemotherapy. Many phase III ADC trials have been initiated based on positive phase I data and although these trials are larger than those conducted historically, prespecified criteria (e.g. patient numbers and magnitude of efficacy) should be met to justify proceeding directly to phase III. Importantly, although several ADCs have been successfully developed without mandatory biomarker selection, biomarker-driven ADC development enables rational patient selection, as illustrated by multiple ADCs (e.g. T-DXd, mirvetuximab soravtansine and telisotuzumab vedotin). The identification, development and validation of predictive biomarkers are therefore essential, particularly given several critical nuances, including the algorithms used to assess biomarker status and the type of specimen analysed, all of which may be influenced by temporal and spatial heterogeneity. Additional ADC research priorities include the optimisation of ADC constructs to enhance efficacy/tolerability and the identification of reliable ADC targets, including work to elucidate attributes of already-identified targets. Finally, considering the vast amount of ADC-related data being generated, artificial intelligence could be leveraged to analyse combined datasets and generate composite biomarkers, including tumour histology, optimal target expression thresholds, molecular alterations and activated pathways affecting payload activity and target function, to accelerate research.

Humans↗

PubMed2022

Lurbinectedin, a selective inhibitor of oncogenic transcription, in patients with pretreated germline BRCA1/2 metastatic breast cancer: results from a phase II basket study.

BACKGROUND: Lurbinectedin, a selective inhibitor of oncogenic transcription, has shown preclinical antitumor activity against homologous recombination repair-deficient models and preliminary clinical activity in BRCA1/2 breast cancer. PATIENTS AND METHODS: This phase II basket multitumor trial (NCT02454972) evaluated lurbinectedin 3.2 mg/m2 1-h intravenous infusion every 3 weeks in a cohort of 21 patients with pretreated germline BRCA1/2 breast cancer. Patients with any hormone receptor and human epidermal growth factor receptor 2 status were enrolled. The primary efficacy endpoint was overall response rate (ORR) according to RECIST v1.1. Secondary endpoints included duration of response (DoR), progression-free survival (PFS), overall survival (OS) and safety. RESULTS: Confirmed partial response (PR) was observed in six patients [ORR = 28.6%; 95% confidence interval (CI) 11.3% to 52.2%] who had received a median of two prior advanced chemotherapy lines. Lurbinectedin was active in both BRCA mutations: four PRs in 11 patients (36.4%) with BRCA2 and two PRs in 10 patients (20.0%) with BRCA1. Median DoR was 8.6 months, median PFS was 4.1 months and median OS was 16.1 months. Stable disease (SD) was observed in 10 patients (47.6%), including 3 with unconfirmed response in a subsequent tumor assessment [ORR unconfirmed = 42.9% (95% CI 21.8% to 66.0%)]. Clinical benefit rate (PR + SD ≥ 4 months) was 76.2% (95% CI 52.8% to 91.8%). No objective response was observed among patients who had received prior poly (ADP-ribose) polymerase inhibitors. The most common treatment-related adverse events (AEs) were nausea (61.9%), fatigue (38.1%) and vomiting (23.8%). These AEs were mostly grade 1/2. The most common grade 3/4 toxicity was neutropenia (42.9%: grade 4, 23.8%: with no febrile neutropenia). CONCLUSIONS: This phase II study met its primary endpoint and showed activity of lurbinectedin in germline BRCA1/2 breast cancer. Lurbinectedin showed a predictable and manageable safety profile. Considering the exploratory aim of this trial as well as previous results in other phase II studies, further development of lurbinectedin in this indication is warranted.

Humans↗