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

Authors

null

Thomas Powles

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

Organizations

Barts Cancer Institute, Experimental Cancer Medicine Centre, Queen Mary University of London, St Bartholomew’s Hospital, London, United Kingdom, Yale Cancer Center, New Haven, CT, Sungkyunkwan University Samsung Medical Center, Seoul, South Korea, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, Medical Oncology Unit, Azienda Ospedaliera S. Maria, Terni, Italy, University Hospital of Besançon, Dept. of Oncology, Besançon, France, Department of Internal Medicine, Chungnam National University School of Medicine, Daejeon, South Korea, Department of Medical Oncology, Beth Israel Deaconess Medical Center; Harvard Medical School, Boston, MA, Yamaguchi University Hospital, Ube, Yamaguchi, Japan, Inova Schar Cancer Institute, Fairfax, VA, Pfizer, Groton, CT, Pfizer, New York, NY, Pfizer, La Jolla, CA, Pfizer srl, Milan, Italy, Gustave Roussy, INSERMU981, Université Paris-Saclay, Villejuif, France, University of Washington, Fred Hutchinson Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA

Research Funding

Pharmaceutical/Biotech Company
Funded by Pfizer as part of an alliance between Merck KGaA, Darmstadt, Germany and Pfizer

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 Details

Meeting

2021 ASCO Annual Meeting

Session Type

Poster Discussion Session

Session Title

Genitourinary Cancer—Kidney and Bladder

Track

Genitourinary Cancer—Kidney and Bladder

Sub Track

Bladder Cancer

Clinical Trial Registration Number

NCT02603432

Citation

J Clin Oncol 39, 2021 (suppl 15; abstr 4520)

DOI

10.1200/JCO.2021.39.15_suppl.4520

Abstract #

4520

Abstract Disclosures