Avelumab first-line (1L) maintenance for advanced urothelial carcinoma (UC): Analysis of clinical and genomic subgroups from the JAVELIN Bladder 100 trial.

Abstract

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Background: In the phase 3 JAVELIN Bladder 100 trial, avelumab 1L maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) vs BSC alone in patients (pts) with advanced UC that had not progressed on 1L platinum-based chemotherapy (HR, 0.69 [95% CI: 0.56, 0.86; 1-sided P= 0.0005]). We report post hoc analyses in previously unreported clinical and genomic subgroups. Methods: In JAVELIN Bladder 100 (NCT02603432), eligible pts had unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L gemcitabine + cisplatin or carboplatin, and were randomized to receive avelumab + BSC (n = 350) or BSC alone (n = 350). The primary endpoint was OS, in all randomized pts and pts with PD-L1+ tumors (Ventana SP263 assay). In this exploratory analysis, we analyzed OS in disease stage and site subgroups, in pts with PD-L1+ tumors who received 1L gemcitabine + carboplatin, and in genomic subtypes (RNAseq whole-transcriptome profiling of tumor tissue) defined using data from The Cancer Genome Atlas (TCGA 2017). Interaction tests were not performed. Results: Prolonged OS was observed in the avelumab + BSC arm vs the BSC alone arm in pts with upper or lower tract tumors, metastatic or locally advanced (LA) and unresectable disease (prior to chemotherapy), and lymph node-only disease post-chemotherapy (Table). OS was also prolonged with avelumab + BSC in pts in PD-L1+ tumors who had received 1L gemcitabine + carboplatin, consistent with findings in the overall population. In genomic subtypes, the OS benefit for avelumab + BSC was apparent across TCGA subtypes except luminal. Conclusions: An OS benefit was seen for avelumab 1L maintenance + BSC vs BSC alone across subgroups of interest. Results are consistent with previously reported findings, further supporting avelumab 1L maintenance as a standard of care for pts with advanced UC that has not progressed with 1L platinum-containing chemotherapy. Clinical trial information: NCT02603432. [Table: see text]