Real world outcomes for maintenance avelumab treatment in locally advanced/metastatic urothelial cancer after platinum-based chemotherapy.
Authors: Rehan Ahmed , Qureshi Muneeb , Goktas Aydin Sabin , O'Connor Kate , Serra Maria , Charnley Natalie , Spurgeon Laura , Muazzam Iqtedar , Bansal Vikram , Vasudev Naveen , Coe Faye , Kagzi Mohammed Mubashir , Din Omar , Leach Diane , Hubbard Rachel , Catto James W.F. , Hussain Syed A. 
Published: January 2024

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Background: Maintenance Avelumab after platinum-based chemotherapy in metastatic-/locally advanced urothelial carcinoma has shown overall and progression free survival benefit in the JAVELIN Bladder 100 trial. We analysed real world outcomes from 6 UK centres. Methods: Retrospective electronic patient records review was carried out for patients treated between January 2021 and September 2023 at 6 UK centres. Patients whose disease had not progressed after platinum-based chemotherapy were started on maintenance avelumab 800mg given at 2 weekly intervals, starting within 12 weeks of last day of chemotherapy as per the National Cancer Drug Fund criteria. Survival outcomes were established using the Kaplan Meier method and compared by a log rank test using SPSS. Results: In total 80 patients (median age 73 years-range 21-86) were included of which 68% were male and 32% were female. 31(38.8%) had prior upper tract and 49(61.2%) had bladder cancers. Metastases were in the nodes only in 33(41.5%) patients whilst 16.9% and 42.3% had bone and visceral metastases respectively. The number of patients with ECOG PS 0,1 and 2 were 36 (45.0%), 33 (41.3%), and 10 (12.5%), respectively. After a median of six cycles of platinum-based chemotherapy, 11.3% had a complete response, and 54.9% had a partial response. Patients then proceeded to maintenance avelumab treatment. Before treatment, the median Neutrophil to Lymphocyte Ratio (NLR) was 2.89. The number of patients with NLR ≤2.89 was 37 (46.3%), and with >2.89 were 38 (47.9%). Median number of cycles were 9 (range 1-66). At a median follow-up of 16.7 months, the median PFS was 8.3 months (95% CI 4.8-15.4). At the data cut-off, 37 patients had died, and 40 patients had progressed. Any grade of adverse event occurred in 34 (42.5%) patients. Grade 3 or higher toxicity rate was 7.5%. Two grade 3 allergic reactions were seen. One patient had Grade 3 immune mediated hepatitis and one patient had grade 3 immune mediated arthritis. Two grade 2 immune mediated colitis were reported. The ORR of avelumab maintenance therapy was 12.5%. 2 patients had a complete response, 8 had a partial response, and 43(53.7%) had stable disease. Within the limit of our small data set, univariate analysis for PFS revealed that there was no significant association between PFS and visceral metastases (p=0.2), bone metastases (p=0.2), node only metastases (p=0.6), primary site(p=0.9), and ECOG PS (p=0.6). However, NLR was a significant prognostic factor for PFS. The median PFS in patients with NLR ≤2.89 vs >2.89 was 16.9 vs 4.2 months, respectively (p=0.001). Conclusions: Our multi centre UK real world data confirms that maintenance Avelumab treatment is well tolerated, and its efficacy data is consistent with previously reported clinical studies.