Abstract：
UNASSIGNED: Nadofaragene firadenovec-vncg is a nonreplicating adenoviral vector-based gene therapy for bacillus Calmette-Guérin (BCG)-unresponsive carcinoma in situ (CIS) with/without high-grade Ta/T1. We report outcomes following 5 years of planned follow-up.
UNASSIGNED: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF).
UNASSIGNED: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease.
UNASSIGNED: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.
UNASSIGNED: This open-label phase 3 trial (NCT02773849) enrolled patients with BCG-unresponsive nonmuscle-invasive bladder cancer in 2 cohorts: CIS ± Ta/T1 (CIS; n = 107) and Ta/T1 without CIS (Ta/T1 cohort; n = 50). Patients received 75 mL (3 × 1011 vp/mL) nadofaragene firadenovec intravesically once every 3 months with cystoscopy and cytology assessments, with continued treatment offered to those remaining high grade recurrence-free (HGRF).
UNASSIGNED: One hundred fifty-seven patients were enrolled from 33 US sites (n = 151 included in efficacy analyses). Median follow-up was 50.8 months (interquartile range 39.1-60.0), with 27% receiving ≥ 5 instillations and 7.6% receiving treatment for ≥ 57 months. Of patients with CIS 5.8% (95% CI 2.2-12.2) were HGRF at month 57, and 15% (95% CI 6.1-27.8) of patients with high-grade Ta/T1 were HGRF at month 57. Kaplan-Meier-estimated HGRF survival at 57 months was 13% (95% CI 6.9-21.5) and 33% (95% CI 19.5-46.6) in the CIS and Ta/T1 cohorts, respectively. Cystectomy-free survival at month 60 was 49% (95% CI 40.0-57.1): 43% (95% CI 32.2-53.7) in the CIS cohort and 59% (95% CI 43.1-71.4) in the Ta/T1 cohort. Overall survival at 60 months was 80% (71.0, 86.0): 76% (64.6-84.5) and 86% (70.9-93.5) in the CIS and Ta/T1 cohorts, respectively. Only 5 patients (4 with CIS and 1 with Ta/T1) experienced clinical progression to muscle-invasive disease.
UNASSIGNED: At 60 months, nadofaragene firadenovec-vncg allowed bladder preservation in nearly half of the patients and proved to be a safe option for BCG-unresponsive nonmuscle-invasive bladder cancer.
摘要：
■Nadofaragenefiradenovec-vncg是一种非复制型基于腺病毒载体的基因疗法，用于治疗有/无HGTa/T1的BCG无反应原位癌（CIS）。我们报告了5年计划随访后的结果。
■这项开放标签的3期试验（NCT02773849）将BCG无反应的NMIBC患者纳入2个队列：CIS±Ta/T1（CIS；n=107）和Ta/T1不包括CIS（Ta/T1队列；n=50）。患者每3个月一次接受75mL（3×1011vp/mL）Nadofaragenefiradenovec膀胱镜检查和细胞学评估，继续为那些仍然没有严重复发（HGRF）的患者提供治疗。
■来自33个美国研究中心的一百五十七名患者（n=151纳入疗效分析）。中位随访时间为50.8个月（IQR39.1-60.0），27%接受≥5次滴注，7.6%接受≥57个月治疗。57个月时，5.8%(95%CI2.2-12.2)的CIS患者和15%(95%CI6.1-27.8)的HGTa/T1患者为HGRF。在CIS和Ta/T1队列中，Kaplan-Meier（KM）估计的57个月HGRF生存率为13％（95％CI6.9-21.5）和33％（95％CI19.5-46.6），分别。60个月时无膀胱切除术生存率为49%（95%CI40.0-57.1）：CIS组43%（95%CI32.2-53.7），Ta/T1组59%（95%CI43.1-71.4）。在CIS和Ta/T1队列中，60个月的总生存率为80％（71.0，86.0）：76％（64.6-84.5）和86％（70.9-93.5），分别。只有5例患者（4例CIS和1例Ta/T1）经历了临床进展为肌肉浸润性疾病。
■60个月时，Nadofaragenefiradenovec-vncg允许近一半的患者保留膀胱，并被证明是BCG无反应的NMIBC的安全选择。
■这项开放标签的3期试验（NCT02773849）将BCG无反应的NMIBC患者纳入2个队列：CIS±Ta/T1（CIS；n=107）和Ta/T1不包括CIS（Ta/T1队列；n=50）。患者每3个月一次接受75mL（3×1011vp/mL）Nadofaragenefiradenovec膀胱镜检查和细胞学评估，继续为那些仍然没有严重复发（HGRF）的患者提供治疗。
■来自33个美国研究中心的一百五十七名患者（n=151纳入疗效分析）。中位随访时间为50.8个月（IQR39.1-60.0），27%接受≥5次滴注，7.6%接受≥57个月治疗。57个月时，5.8%(95%CI2.2-12.2)的CIS患者和15%(95%CI6.1-27.8)的HGTa/T1患者为HGRF。在CIS和Ta/T1队列中，Kaplan-Meier（KM）估计的57个月HGRF生存率为13％（95％CI6.9-21.5）和33％（95％CI19.5-46.6），分别。60个月时无膀胱切除术生存率为49%（95%CI40.0-57.1）：CIS组43%（95%CI32.2-53.7），Ta/T1组59%（95%CI43.1-71.4）。在CIS和Ta/T1队列中，60个月的总生存率为80％（71.0，86.0）：76％（64.6-84.5）和86％（70.9-93.5），分别。只有5例患者（4例CIS和1例Ta/T1）经历了临床进展为肌肉浸润性疾病。
■60个月时，Nadofaragenefiradenovec-vncg允许近一半的患者保留膀胱，并被证明是BCG无反应的NMIBC的安全选择。
