12070 Background: Testicular cancer (TC) treatment has been associated with cardiovascular disease (CVD) development. To facilitate development of preventive strategies, this study assessed risk factors associated with CVD in TC survivors. Methods: Incidence of coronary artery disease, myocardial infarction and heart failure was assessed in a multicenter cohort comprising 4,748 TC survivors treated at ages of 12-50 years between 1976-2007. Patients who developed CVD and a random sample from the cohort received a questionnaire on cardiovascular risk factors (CVRF) and quality of life (QoL, measured with SF-36). A subgroup (n=304) of responders in the cohort additionally underwent clinical evaluation of CVRF. Results: After a median follow-up of 16 years, 272 patients developed CVD. Compared to orchidectomy only, platinum-based chemotherapy was associated with increased CVD risk (Hazard Ratio (HR) 1.8, 95% Confidence Interval(CI) 1.3-2.5). CVD risk was increased among patients who were obese or a smoker at diagnosis (HR 4.7, 95%CI 2.4-9.3 and HR 1.5, 95%CI 1.1-2.2, respectively) and patients with Raynaud's phenomenon (HR 1.9, 95%CI 1.1-3.6) or a family history of CVD (HR 2.7, 95%CI 1.6-4.5). TC survivors with CVD reported inferior QoL on physical domains (table). In TC survivors who underwent clinical evaluation for CVRF (median age at assessment 51 years), 86% had dyslipidemia, 50% hypertension and 35% metabolic syndrome, irrespective of treatment. Conclusions: TC survivors treated with platinum-based chemotherapy, who were obese or smoking at diagnosis, had family history of CVD and who developed Raynaud’s phenomenon are at risk to develop CVD, which affects QoL. Many TC survivors carry undetected CVRF. We advocate early lifestyle adjustments and lifelong follow-up with low-threshold treatment of CVRF, especially in obese and smoking patients treated with platinum-based chemotherapy. [Table: see text]
LBA443 Background: The 2 primary endpoints of the CheckMate 274 trial were met as nivolumab (NIVO) improved disease-free survival (DFS) versus placebo (PBO) in the intent-to-treat (ITT) population and in patients with tumor programmed death ligand 1 (PD-L1) expression ≥ 1%. We report extended follow-up data. Methods: CheckMate 274 is a phase 3, double-blind trial of adjuvant NIVO versus PBO for high-risk muscle-invasive urothelial carcinoma (MIUC) (bladder, ureter, or renal pelvis) after radical resection. Patients were randomly assigned 1:1 to NIVO 240 mg every 2 wk or PBO for ≤ 1 year of treatment. Patients had pathologic evidence of UC at high risk of recurrence and Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 1. Primary endpoints were DFS in ITT patients and in patients with PD-L1 ≥ 1%. DFS was also analyzed in prespecified subgroups. Overall survival and non–urothelial tract recurrence-free survival (NUTRFS) in ITT patients and in patients with PD-L1 ≥ 1% were secondary endpoints. Distant metastasis-free survival (DMFS) and safety were exploratory endpoints. Results: There were 353 patients randomly assigned to NIVO (PD-L1 ≥ 1%, n = 140) and 356 to PBO (PD-L1 ≥ 1%, n = 142). With median follow-up of 36.1 months (minimum follow-up, 31.6 months), median DFS was 22.0 months with NIVO versus 10.9 months with PBO in ITT patients and 52.6 months with NIVO versus 8.4 months with PBO in patients with PD-L1 ≥ 1% (Table). DFS benefit was seen in most subgroups analyzed including age, sex, ECOG PS, nodal status, prior cisplatin-based chemotherapy, and PD-L1 status. NUTRFS and DMFS benefits with NIVO versus PBO were also observed in both populations (Table). Grade 3–4 treatment-related adverse events occurred in 18.2% and 7.2% of patients in the NIVO and PBO arms, consistent with the primary analysis. Overall survival will be assessed at a future database lock. Conclusions: With extended follow-up, NIVO continued to show DFS, NUTRFS, and DMFS benefits versus PBO. The hazard ratio (HR) for DFS and NUTRFS in PD-L1 ≥ 1% patients and for DMFS in both ITT and PD-L1 ≥ 1% patients also continued to improve versus the primary analysis. No new safety signals were identified. These results further support adjuvant NIVO as a standard of care for high-risk MIUC after radical resection. Clinical trial information: NCT02632409 . [Table: see text]
TPS583 Background: Treatment options are limited for pts with NMIBC and MIBC who experience disease recurrence or who are ineligible for or refuse standard of care. Erda, an oral selective pan-FGFR tyrosine kinase inhibitor, is approved in adults with locally advanced or metastatic urothelial cancer with select FGFR3/2 alterations ( alt) who have progressed during or after ≥1 line of platinum-containing chemotherapy. FGFRalt are among the most common oncogenic drivers detected in NMIBC and MIBC, and are more prevalent in NMIBC. TAR-210 is an intravesical drug delivery system designed to provide local, continuous release of erda within the bladder, thus limiting systemic toxicity. This study evaluates the safety, pharmacokinetics (PK), and efficacy of TAR-210 in pts with NMIBC or MIBC with select FGFRalt. Methods: Open-label, multicenter phase 1 study of TAR-210 in pts with recurrent NMIBC or MIBC (NCT05316155). Eligible pts are aged ≥18 yrs with adequate organ function and tumors with select FGFRalt. A flexible molecular eligibility strategy is used to allow for local or central fresh/archival tissue-based FGFR testing by next-generation sequencing (NGS) or PCR, or urine cell-free DNA NGS testing. Four cohorts will be enrolled: pts with recurrent, bacillus Calmette-Guerin (BCG)-experienced papillary-only high-risk (HR) NMIBC (high-grade Ta/T1) refusing or ineligible for radical cystectomy (RC) (Cohort 1) or scheduled for RC (Cohort 2); pts with recurrent, intermediate-risk NMIBC (Ta/T1) with a history of low-grade disease (Cohort 3); pts with cT2-T3a MIBC scheduled for RC refusing or ineligible for neoadjuvant cisplatin (Cohort 4). Pts in Cohorts 1 and 2 will have TURBT with resection of all visible disease prior to dosing, whereas pts in Cohort 3 must have visible disease prior to dosing. The primary end point is safety (adverse events, including dose-limiting toxicity). Secondary end points include PK, recurrence-free survival (Cohorts 1 and 2), complete response (CR) rate and duration of CR (Cohort 3), and pathologic CR rate, pT0 rate, and rate of downstaging to <pT2 (Cohort 4). Dose escalation (Part 1; n≈12, Cohorts 1 and 3 only) will be followed by dose expansion (Part 2; n≈50-80). Cohorts 1 and 3: response assessment will be after a 3-mo dosing cycle; pts with CR may receive ≤3 additional 3-mo dosing cycles if no recurrence, progression, or unacceptable toxicity. Cohorts 2 and 4: response assessment will be at RC after 8 wks of dosing. Follow-up disease surveillance (cystoscopy, urine cytology, imaging) will be every 3 mos to end of Yr 2 and every 6 mos in Yr 3 in Cohorts 1 and 3 and at 3 mos post-RC in Cohorts 2 and 4. Four pts were enrolled since April 2022 (1 in Cohort 1, 3 in Cohort 3); enrollment for Cohorts 2 and 4 is planned soon. Clinical trial information: NCT05316155 .
TPS585 Background: Standard of care for MIBC is neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy + pelvic lymph node dissection (RC + PLND). However, a substantial proportion of patients (pts) with MIBC are ineligible to receive cisplatin-based chemotherapy. In the phase 1b/2 KEYNOTE-869/EV-103 study, promising antitumor activity was shown in cisplatin-ineligible pts with metastatic urothelial carcinoma treated with the PD-1 inhibitor pembro combined with the nectin-4–directed antibody-drug conjugate EV. This multicenter, open-label, randomized, phase 3 KEYNOTE-905/EV-303 study (NCT03924895) is designed to evaluate the efficacy and safety of perioperative pembro alone or in combination with EV compared with RC + PLND alone in pts with MIBC who are ineligible for or decline cisplatin-based treatment. Methods: Approximately 857 adults who are cisplatin ineligible or decline cisplatin-based treatment with treatment-naive MIBC (T2-T4aN0M0 or T1-T4aN1M0), have an Eastern Cooperative Oncology Group performance status score of 0-2, and have a predominant (≥50%) urothelial histology will be randomly assigned to arm A (neoadjuvant pembro 200 mg intravenously [IV] every 3 weeks [Q3W] up to 3 cycles followed by RC + PLND and adjuvant pembro 200 mg IV Q3W up to 14 cycles), arm B (RC + PLND followed by observation), or arm C (neoadjuvant EV 1.25 mg/kg + pembro 200 mg IV Q3W up to 3 cycles followed by RC + PLND and adjuvant EV + pembro up to 6 cycles and adjuvant pembro 200 mg IV Q3W up to 8 cycles). In both the neoadjuvant and adjuvant phases of arm C, pembro will be administered on day 1 and EV will be administered on days 1 and 8 of each cycle. Dual primary end points are pathologic complete response as assessed by central pathologic review and event-free survival. Secondary end points include overall survival, disease-free survival, pathologic downstaging rates, and safety and tolerability. Enrollment is ongoing in Africa, Asia, Europe, and North America. Clinical trial information: NCT03924895 .
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