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).
Authors: Antonuzzo Lorenzo , Maruzzo Marco , De Giorgi Ugo , Santini Daniele , Tambaro Rosa , Buti Sebastiano , Carrozza Francesco , Calabrò Fabio , Di Lorenzo Giuseppe , Fornarini Giuseppe , Iacovelli Roberto , Cullurà Daniela , Messina Carlo , Masi Claudia , Ciccia Angelo , Fazzi Gennaro , Venturini Filippo , Colasanto Raffaele , Necchi Andrea , Bracarda Sergio 
Published: March 2023

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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.