704MO - Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone with 1L chemotherapy (CTx) for advanced urothelial carcinoma (UC): Subgroup analyses from JAVELIN Bladder 100

Background

In the phase 3 JAVELIN Bladder 100 trial (NCT02603432), avelumab (anti–PD-L1) 1L maintenance + BSC significantly prolonged overall survival (OS) vs BSC alone in patients (pts) with advanced UC without disease progression with 1L induction CTx (gemcitabine + cisplatin [GemCis] or carboplatin [GemCar]) in all randomized pts (hazard ratio [HR] 0.69; p=0.0005) and pts with PD-L1+ tumors (HR 0.56; p=0.0003). We report prespecified subgroup analyses.

Methods

Pts were randomized 1:1 to avelumab + BSC or BSC alone, stratified by best response to 1L CTx (complete/partial response [CR/PR] vs stable disease [SD]) and by visceral vs nonvisceral disease. The primary endpoint was OS (from randomization). PD-L1 status was assessed using the Ventana SP263 assay.

Results

700 pts were randomized to either avelumab + BSC (n=350) or BSC alone (n=350); median follow-up was >19 mo. An OS benefit with avelumab + BSC vs BSC alone (median [95% CI], mo) was observed across prespecified subgroups, including pts with objective response (CR/PR; 23.8 [19.0, not estimable (NE)] vs 15.0 [13.0, 18.7]; HR 0.69 [0.53, 0.89]) or SD (19.9 [18.2, NE] vs 14.0 [10.7, 19.4]; HR 0.70 [0.46, 1.05]) as best response to 1L CTx; and pts with visceral (18.9 [16.5, 21.4] vs 14.0 [11.7, 17.4]; HR 0.82 [0.62, 1.09]) and nonvisceral metastases (28.3 [23.8, NE] vs 15.2 [13.4, 20.2]; HR 0.54 [0.38, 0.76]). OS in other subgroups is shown (Table). No significant treatment-by-subgroup interaction (at 0.05 level) was observed for any subgroup variable. Additional subgroups, progression-free survival, objective response endpoints, and safety data will also be presented.

Conclusions

Avelumab 1L maintenance + BSC provided OS benefit vs BSC alone across prespecified subgroups of pts whose disease had not progressed with 1L induction CTx and is an important advance for 1L treatment of advanced UC. Table: 704MO

*Wald Chi-sq. test, 2 sided.

Clinical trial identification

NCT02603432.

Editorial acknowledgement

Medical writing support was provided by Kelly Bryant of ClinicalThinking (Hamilton, NJ, USA) and funded by Pfizer and Merck KGaA, Darmstadt, Germany.

Legal entity responsible for the study

Pfizer.

Funding

This study was sponsored by Pfizer, and is part of an alliance between Pfizer and Merck KGaA, Darmstadt, Germany.

Disclosure

P. Grivas: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Bavarian Nordic; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Biocept; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution), Travel/Accommodation/Expenses, Educational unbranded activity with Bristol-Myers Squibb (2017): Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Clovis Oncology; Research grant/Funding (institution): Debiopharm; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Driver; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: EMD Serono; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Exelixis; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Foundation Medicine; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech; Honoraria (self), Advisory/Consultancy: GlaxoSmithKline; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Heron Therapeutics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Mirati Therapeutics; Research grant/Funding (institution): Oncogenex; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Pfizer; Research grant/Funding (institution): Immunomedics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Seattle Genetics; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: QED Therapeutics; Honoraria (institution): KureIT. C. Caserta: Advisory/Consultancy: Janssen; Advisory/Consultancy: Merck; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Novartis Pharma SAS; Advisory/Consultancy: Pfizer Pharmaceuticals Israel. B. Perez Valderrama: Advisory/Consultancy, Non-remunerated activity/ies: Astellas Pharma; Advisory/Consultancy, Non-remunerated activity/ies: Bristol-Myers Squibb; Advisory/Consultancy, Non-remunerated activity/ies: Ipsen; Advisory/Consultancy: Pierr-Fabre; Advisory/Consultancy: Bayer; Advisory/Consultancy, Non-remunerated activity/ies: Roche; Advisory/Consultancy: Sanofi; Advisory/Consultancy: EUSA Pharma; Advisory/Consultancy: MSD Oncology; Advisory/Consultancy: Novartis Pharma SAS; Non-remunerated activity/ies: Pfizer Pharmaceuticals Israel. H. Gurney: Advisory/Consultancy: BMS; Advisory/Consultancy: MSD; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Roche; Advisory/Consultancy: Ipsen; Advisory/Consultancy: AstraZeneca. Y. Loriot: Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: Janssen; Advisory/Consultancy, Travel/Accommodation/Expenses: Astellas. S.S. Sridhar: Advisory/Consultancy: Astellas Pharma; Advisory/Consultancy, Research grant/Funding (institution): Janssen; Advisory/Consultancy: Sanofi; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Advisory/Consultancy: Roche/Genentech; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Merck; Advisory/Consultancy, Research grant/Funding (institution): Pfizer. N. Tsuchiya: Honoraria (self): Astellas; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Janssen; Honoraria (self): Novartis; Honoraria (self): Ono; Honoraria (self): Bayer; Honoraria (self): Sanofi; Honoraria (self): Takeda; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): MDS. S. Gupta: Honoraria (self), Speaker Bureau/Expert testimony: Exelixis; Honoraria (self), Speaker Bureau/Expert testimony: Janssen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): BMS; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Honoraria (self), Advisory/Consultancy: AstraZeneca; Research grant/Funding (institution): Astellas. B. Huang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. N. Costa: Full/Part-time employment: Pfizer. J.A. Blake-Haskins: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. A. di Pietro: Shareholder/Stockholder/Stock options, Full/Part-time employment: Pfizer. T.B. Powles: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Genentech/Roche; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Novartis; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Advisory/Consultancy, Travel/Accommodation/Expenses: Ipsen; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Pfizer; Advisory/Consultancy: Incyte; Honoraria (self), Advisory/Consultancy: Seattle Genetics; Travel/Accommodation/Expenses: MSD; Travel/Accommodation/Expenses: Research to Practice; Honoraria (self), Travel/Accommodation/Expenses: Ferring; Honoraria (self): Gerson Lehrman Group; Honoraria (self): Janssen Research & Development. All other authors have declared no conflicts of interest.