Indications For Local Therapy Research Articles

Abstract PO2-04-05: FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES

Abstract Background Brain metastases (BM) are a severe complication of HER2-positive metastatic breast cancer. In the absence of any immediate indication for local therapy, the tyrosine-kinase inhibitor tucatinib combined with trastuzumab and capecitabine (TTC) is regarded as the preferred systemic treatment option for active BM, while data on the activity of antibody-drug conjugates (ADC) is limited. In the primary outcome analysis of TUXEDO-1, an intracranial response rate (RR) of 73.3% was reported with the ADC trastuzumab-deruxtecan (T-DXd). Here, we report final progression-free survival (PFS) and overall survival (OS) results of this study. Patients and Methods: TUXEDO-1 is a prospective, single-centre, single-arm phase 2 trial. Adult patients with HER2-positive BC and active BM (newly diagnosed untreated or progressing after prior local therapy), prior treatment with trastuzumab and pertuzumab, ECOG performance status 0 or 1 without indication for immediate local therapy were accrued and received T-DXd until progression, inacceptable toxicity, or withdrawal for any other reason. The primary endpoint was intracranial RR centrally assessed by Response Assessment in Neuro-Oncology (RANO)-BM criteria in the intention-to-treat population; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population (PPP). Results A total number of 15 patients were accrued; one patient was found to have dural metastases only upon restaging, resulting in a PPP of 14 patients. Patients had received a median number of two prior treatment lines (range, 1-5), 60% had progressive brain metastases and 60% had received prior T-DM1. At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). A total of 238 cycles of T-DXd were administered (median 11.5 cycles; range 4-42). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event (AE) was fatigue (n=3; 20%). A total of 8 serious AEs were reported in 8 patients. Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL and neurocognitive functioning were maintained over the entire treatment duration and a significant deterioration of global QoL was observed upon progression (p=0.036). Most patients received TTC (n=5) or local therapy (n=4) as next subsequent treatment line. Ancillary biomarker studies are ongoing, and results will be presented at the meeting. Discussion In TUXEDO-1, T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive breast cancer BM. The safety profile was consistent with previous reports. T-DXd did not impair QoL and neurocognitive functioning was maintained. Results therefore support the concept of ADCs as systemic therapy for active BM. Citation Format: Rupert Bartsch, Anna Sophie Berghoff, Julia Furtner, Maximilian Marhold, Elisabeth Sophie Bergen, Sophie Roider-Schur, Angelika Maria Starzer, Maximilian Mair, Heidrun Forstner, Beate Rottenmanner, Marie-Bernadette Aretin, Karin Dieckmann, Zsuzsanna Bago-Horvath, Helmuth Haslacher, Georg Widhalm, Aysegül Ilhan-Mutlu, Christoph Minichsdorfer, Thorsten Fuereder, Thomas Szekeres, Leopold Oehler, Birgit Gruenberger, Georg Pfeiler, Christian F. Singer, Ansgar Weltermann, Luzia Berchtold, Matthias Preusser. FINAL OUTCOME ANALYSIS FROM THE PHASE II TUXEDO-1 TRIAL OF TRASTUZUMAB-DERUXTECAN IN HER2-POSITIVE BREAST CANCER PATIENTS WITH ACTIVE BRAIN METASTASES [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-04-05.

Intravitreal Clindamycin and Dexamethasone for Zone 1 Toxoplasmic Retinochoroiditis at Twenty-four Months

To report the anatomic and functional outcomes of intravitreal clindamycin and dexamethasone for the treatment of zone 1 toxoplasmic retinochoroiditis (TRC). Patients had 1 or more of the following indications for local therapy: intolerance to oral medication, contraindication to oral medication because of pregnancy, lack of response despite oral antimicrobial treatment, or treatment with concomitant oral and local therapy to avoid or limit foveal or optic disc involvement. Noncomparative, retrospective, multicentric interventional case series. We reviewed the medical records of 12 consecutive patients (eyes) with posterior pole (zone 1) TRC who were treated weekly or every 4 weeks (during pregnancy) with intravitreal injections of clindamycin (1.5 mg/0.1 ml) and dexamethasone (400 microg/0.1 ml). Ophthalmic evaluation included Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA); assessment of central macular thickness (CMT); resolution of inflammation by optical coherence tomography (OCT), clinical examination, and fluorescein angiography; and assessment of adverse events. Patients were followed for 24 months. Resolution of TRC, changes in BCVA, and OCT. Resolution of TRC was achieved in all cases with a mean number of injections of 3.6 (range: 2-5 injections) with a mean interval of 15.5+/-4 days. At 24 months a significant reduction in CMT by OCT was observed, from 387.6+/-70.1 microm to 185.2+/-44.7 microm (P = 0.0004). Baseline BCVA was logarithm of the minimal angle of resolution (logMAR) 1+/-0.4 (20/200), which improved to 0.5+/-0.4 (20/63) (P = 0.002) at the end of follow-up. Ten eyes (83.3%) improved > or =2 ETDRS lines of BCVA, and 2 eyes (20%) remained stable at 24 months. One patient's vision was limited because of macular scarring. No ocular or systemic adverse events were observed. No recurrences at 24 months of follow-up were observed. The combination of intravitreal clindamycin and dexamethasone was associated with resolution of zone 1 TRC and functional and anatomic improvement in patients who did not tolerate, had contraindications to, or did not respond to oral medications.