READY: Real-world data from an Italian compassionate use program of avelumab first-line maintenance (1LM) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC).
READY: Real-world data from an Italian compassionate use program of avelumab first-line maintenance (1LM) treatment for locally advanced or metastatic urothelial carcinoma (la/mUC).
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准备就绪：来自意大利 avelumab 一线维持 (1LM) 治疗局部晚期或转移性尿路上皮癌 (la/mUC) 同情使用计划的真实世界数据。
DOI：
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发表时间：
2023
影响因子：
45.3
通讯作者：
S. Bracarda
中科院分区：
文献类型：
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作者：
L. Antonuzzo;M. Maruzzo;U. de Giorgi;D. Santini;R. Tambaro;S. Buti;F. Carrozza;F. Calabrò;G. Di Lorenzo;G. Fornarini;R. Iacovelli;D. Cullurà;C. Messina;Claudia Masi;Angelo Ciccia;G. Fazzi;F. Venturini;Raffaele Colasanto;A. Necchi;S. Bracarda
469背景：在JAVELIN膀胱100的3期试验（NCT02603432）中，avelumab（抗pd - l1） 1LM加最佳支持治疗（BSC）在1 l铂基化疗（PBC）后疾病没有进展的la/mUC患者（pts）中显著延长了总生存期（OS），目前在国际上被推荐为1级证据的标准治疗。我们报告了来自大型、多中心、意大利同情使用项目（CUP）的真实世界描述性pt特征和结果数据，该项目评估了la/mUC患者的avelumab 1LM。该前瞻性非介入性CUP于2021年1月18日启动，旨在为la/mUC患者在意大利药品管理局报销之前提供早期获得avelumab的机会。Avelumab是应医生要求提供的，并经当地伦理委员会批准，符合意大利同情使用法规。根据当地处方信息，对PBC后无进展的≥18岁la/mUC成年患者每2周给予Avelumab 800mg IV（4-6个周期，在最后一次给药后4-10周开始）。先前的辅助或新辅助全身治疗（包括免疫检查点抑制剂）在12个月内复发的患者不符合条件。结果：截至2022年8月16日，从2021年1月至2022年3月，从140个意大利中心纳入了464名患者（78.4%为男性，21.6%为女性）。纳入时的中位年龄为70岁（IQR， 63-76岁）。在1L PBC开始时，346例（73.9%）患者有转移性疾病，40例（8.6%）患者有不可切除的局部晚期疾病（78例（16.8%）患者的疾病分期未确定[N/D]）。321例患者ECOG PS为0(69.2%)，140例患者ECOG PS为1(30.2%)，3例患者ECOG PS为N/D（0.7%）。原发肿瘤部位为上呼吸道148例（31.9%），下呼吸道309例（66.6%）（N/D 7例[1.5%]）。1L PBC包括卡铂+吉西他滨241例（51.9%），顺铂+吉西他滨214例（46.1%），其他PBC 9例（1.9%）；225例（48.5%）接受了4个周期的PBC治疗，54例（11.6%）接受了5个周期的PBC治疗，177例（38.2%）接受了6个周期的PBC治疗（其他或无/无8例[1.7%]）。51例（11.0%）患者对1L PBC达到完全缓解，266例（57.3%）患者达到部分缓解，147例（31.7%）患者病情稳定。对于391名患者，目前可评估的OS和无进展生存期（PFS）从avelumab开始，12个月的OS率为69.1% (95% CI, 64.4%-73.6%)，而中位OS未达到。12个月PFS率为38.9% (95% CI, 34.0%-43.7%)，中位PFS为6.6个月（95% CI, 5.6-8.9个月）。发生3-4级不良事件33例（7.1%）。结论：该CUP纳入了140个意大利肿瘤中心日常临床实践的大量pt人群，结果与先前的研究一致。总的来说，这些真实世界的数据加强了JAVELIN膀胱100的发现，并进一步支持avelumab 1LM作为la/mUC患者的标准治疗。
469 Background: In the phase 3 JAVELIN Bladder 100 trial (NCT02603432), avelumab (anti–PD-L1) 1LM plus best supportive care (BSC) in patients (pts) with la/mUC whose disease did not progress after 1L platinum-based chemotherapy (PBC) significantly extended overall survival (OS) vs BSC alone, and it is now recommended internationally as standard of care with level 1 evidence. We report real-world descriptive pt characteristics and outcomes data from a large, multicenter, Italian compassionate use program (CUP) assessing avelumab 1LM in pts with la/mUC. Methods: This prospective, noninterventional CUP was initiated on Jan 18, 2021, to provide early access to avelumab before reimbursement by the Italian Medicines Agency for pts with la/mUC. Avelumab was provided upon physician request and after approval by local ethics committees in accordance with the Italian compassionate use regulation. Avelumab 800 mg IV was administered every 2 weeks per local prescribing information to adult pts aged ≥18 years with la/mUC who were progression-free following PBC (4-6 cycles, starting 4-10 weeks after last dose of PBC). Pts who had a relapse within 12 months of prior adjuvant or neoadjuvant systemic therapy, including immune checkpoint inhibitors, were not eligible. Results: As of Aug 16, 2022, 464 pts (78.4% male, 21.6% female) were included from 140 Italian centers from Jan 2021-Mar 2022. Median age at inclusion was 70 years (IQR, 63-76 years). At the start of 1L PBC, 346 pts (73.9%) had metastatic disease and 40 (8.6%) had unresectable locally advanced disease (disease stage not defined [N/D] in 78 pts [16.8%]). ECOG PS was 0 in 321 pts (69.2%), 1 in 140 (30.2%), and N/D in 3 (0.7%). Primary tumor site was upper tract in 148 pts (31.9%) and lower tract in 309 (66.6%) (N/D in 7 [1.5%]). 1L PBC comprised carboplatin + gemcitabine in 241 pts (51.9%), cisplatin + gemcitabine in 214 (46.1%), and other PBC in 9 (1.9%); 225 pts (48.5%) received 4 cycles of PBC, 54 (11.6%) received 5 cycles, and 177 (38.2%) received 6 cycles (other or N/D in 8 [1.7%]). Complete response to 1L PBC was achieved in 51 pts (11.0%), partial response in 266 (57.3%), and stable disease in 147 (31.7%). For 391 pts currently evaluable for OS and progression-free survival (PFS) from the start of avelumab, the 12-month OS rate was 69.1% (95% CI, 64.4%-73.6%), while median OS was not reached. The 12-month PFS rate was 38.9% (95% CI, 34.0%-43.7%) and median PFS was 6.6 months (95% CI, 5.6-8.9 months). Grade 3-4 adverse events occurred in 33 pts (7.1%). Conclusions: This CUP included a large pt population representative of daily clinical practice in 140 Italian oncology centers and the results are consistent with those of previous studies. Overall, these real-world data strengthen the findings of JAVELIN Bladder 100 and provide further support for avelumab 1LM as a standard of care in eligible pts with la/mUC.