Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew’s Hospital, London, United Kingdom
Thomas Powles , Daniel P. Petrylak , Se Hoon Park , Srikala S. Sridhar , Claudia Caserta , Antoine Thiery Vuillemin , Hyo Jin Lee , Joaquim Bellmunt , Yoshiaki Yamamoto , Jeanny B. Aragon-Ching , Bo Huang , Keith A. Ching , Craig B. Davis , Alessandra Di Pietro , Yohann Loriot , Petros Grivas
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
Subgroup | Pts, n | Median OS (95% CI), months | HR (95% CI) | ||
---|---|---|---|---|---|
Avelumab + BSC | BSC | Avelumab + BSC | BSC | ||
Upper tract | 106 | 81 | 19.9 (15.3, NE) | 17.4 (12.8, 33.0) | 0.89 (0.578, 1.373) |
Lower tract | 244 | 269 | 22.5 (19.0, 28.3) | 14.1 (11.8, 17.9) | 0.62 (0.477, 0.802) |
Metastatic disease | 216 | 215 | 18.2 (13.8, 20.3) | 14.1 (11.7, 17.3) | 0.88 (0.678, 1.147) |
LA and unresectable disease | 133 | 133 | NE (25.3, NE) | 17.9 (13.5, NE) | 0.40 (0.265, 0.617) |
Lymph node-only disease* | 48 | 39 | NE (23.8, NE) | NE (10.7, NE) | 0.55 (0.259, 1.152) |
1L gemcitabine + carboplatin, PD-L1+ tumor | 74 | 54 | 24.0 (18.6, NE) | 16.1 (9.4, NE) | 0.67 (0.393, 1.137) |
TCGA: basal squamous | 45 | 44 | 24.0 (16.0, NE) | 17.9 (12.7, NE) | 0.62 (0.326, 1.187) |
TCGA: luminal | 30 | 25 | 23.8 (12.5, NE) | NE (14.3, NE) | 1.01 (0.403, 2.509) |
TCGA: luminal infiltrated | 143 | 143 | 19.9 (18.2, NE) | 14.3 (12.8, 18.6) | 0.68 (0.481, 0.968) |
TCGA: luminal papillary | 61 | 63 | 22.5 (18.2, 26.0) | 13.4 (10.1, NE) | 0.63 (0.370, 1.079) |
NE, not estimable *Post-chemotherapy.
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Abstract Disclosures
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