Aims: In JAVELIN Bladder 100 (NCT02603432), avelumab first-line maintenance + best supportive care (BSC) significantly prolonged overall survival (OS) vs BSC alone in patients with advanced urothelial carcinoma (UC) not progressed with first-line platinum-based chemotherapy (HR, 0.69 [95% CI: 0.56, 0.86; 1-sided P=0.0005]). We report post hoc analyses in clinical and genomic subgroups.
Methods: Patients with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of first-line gemcitabine + carboplatin (GemCar) or gemcitabine + cisplatin were randomized to receive avelumab + BSC (n=350) or BSC alone (n=350). The primary endpoint was OS, assessed in all randomized patients and patients with PD-L1+ tumors (Ventana SP263). This exploratory analysis evaluated OS in subgroups defined by primary tumor or type of advanced disease, in patients with PD-L1+ tumors treated with first-line GemCar, and in genomic subtypes (RNAseq whole-transcriptome profiling of tumor tissue) per The Cancer Genome Atlas (TCGA 2017).
Results: Prolonged OS was observed with avelumab + BSC vs BSC alone (HR [95% CI]) in patients with upper or lower tract tumors (0.89 [0.578, 1.373] and 0.62 [0.477, 0.802]); metastatic or locally advanced and unresectable disease prior to chemotherapy (0.88 [0.678, 1.147] and 0.40 [0.265, 0.617]), or lymph node-only disease post-chemotherapy (0.55 [0.259, 1.152]); and patients with PD-L1+ tumors who had received first-line GemCar (0.67 [0.393, 1.137]). An OS benefit for avelumab + BSC was apparent in TCGA subtypes basal squamous (0.62 [0.326, 1.187]), luminal infiltrated (0.68 [0.481, 0.968]) and luminal papillary (0.63 [0.370, 1.079]) but not luminal (1.01 [0.403, 2.509]).
Conclusions: An OS benefit was seen for avelumab first-line maintenance + BSC vs BSC alone across subgroups of interest. Results are consistent with previously reported findings, further supporting avelumab first-line maintenance as a standard of care for patients with advanced UC that has not progressed with first-line platinum-based chemotherapy.