Abstract 757P
Background
Pts with FGFRa (mutations/fusions) may respond suboptimally to immune checkpoint inhibitors. We retrospectively assessed the effects of prespecified FGFRa (corresponding to those evaluated in erdafitinib studies) in pts with locally advanced/metastatic UC and prior anti-PD-(L)1 therapy.
Methods
In this noninterventional, multicenter (5 US sites, 3 European sites) study, outcomes by FGFRa status in pts with any line of prior anti-PD-(L)1 therapy but without prior FGFR inhibitor were assessed using routine clinical practice data (collected May 2018-July 2019). Investigator-determined objective response rate (ORR), disease control rate (DCR), and overall survival (OS, per multivariate and unadjusted analyses) were assessed.
Results
Of 94 pts, 38 were FGFRa+ and 56 were FGFRa-. Demographics and baseline characteristics were similar among those pts. Response rate to PD-(L)1 therapy trended lower for FGFRa+ vs FGFRa- pts regardless of prior chemotherapy. Median OS was shorter for FGFRa+ vs FGFRa- pts with any line of PD-(L)1 (Table). ORR and DCR and trends in OS were generally consistent regardless of line of therapy. Multivariate analysis confirmed trends for shorter OS for FGFRa+ pts (hazard ratio [HR], 1.85 [95% confidence interval, 0.98-3.49]; p = 0.057). Only for pts with prior platinum chemotherapy and then anti-PD-(L)1 OS was shorter and ORR and DCR were lower for FGFRa+ pts. Table: 757P
| FGFRa+ | FGFRa- | p Value | |
| Pts with any line anti-PD-(L)1, n | 38 | 54 | |
| ORR, % (95% CI) | 16 (4.2-27.4) | 26 (14.2- 37.6) | |
| DCR, % (95% CI) | 29 (14.5-43.4) | 52 (38.5- 65.2) | NS |
| OS, months (95% CI) | 8.6 (6.1-18.3) | 13.2 (7.3- 39.2) | 0.05 |
| Pts with prior platinum and subsequent any line anti-PD-(L)1, n | 25 | 40 | |
| ORR, % (95% CI) | 12 (0.0-24.7) | 25 (11.6-38.4) | NS |
| DCR, % (95% CI) | 28 (10.4-45.6) | 53 (37.0-68.0) | NS |
| OS, months (95% CI) | 7.5 (5.5-19.7) | 11.4 (5.4-22.0) | NS |
OS data from unadjusted analyses are provided in median months.ORR data are provided in n (%).NE, not estimable; NS, not statistically significant.
Conclusions
In this retrospective observational study of pts with advanced UC with prior PD-(L)1 therapy, ORR and DCR trended lower for FGFRa+ pts. By multivariate analysis, OS was shorter in FGFRa+ pts. A phase 3 study (NCT03390504) of FGFR-directed therapy vs anti PD-(L)1 therapy in FGFRa+ pts is ongoing to prospectively validate findings.
Clinical trial identification
Editorial acknowledgement
Sally Hassan PhD, CMPP of Parexel International provided editorial assistance for this abstract.
Legal entity responsible for the study
Janssen Research & Development, LLC.
Funding
Janssen Research & Development, LLC.
Disclosure
A. Rezazadeh: Advisory/Consultancy: Exelixis, AstraZeneca, Bayer, Pfizer, Novartis, Genentech, Bristol Myers Squibb, EMD Serono; Speaker Bureau/Expert testimony: Janssen, Astellas Medivation, Pfizer, Novartis, Genentech/Roche, Eisai, AstraZeneca, Bristol Myers Squibb, Amgen, Exelixis, EMD Serono, Merck, Seattle Genetics/Astellas; Research grant/Funding (institution): Genentech, Exelixis, Janssen, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Macrogenics, Astellas Pharma, Beyond Spring, BioClin Therapeutics, Clovis Oncology, Bavarian Nordic, Seattle Genetics, Immunomedics, Epizy; Travel/Accommodation/Expenses: Genentech, Prometheus Labratories, Astellas Medivation, Janssen, Eisai, Bayer, Pfizer, Novartis, Exelixis, AstraZeneca. Y. Loriot: Honoraria (self): Roche, Astellas, Janssen, Seattle Genetics, Astra-Zeneca, Bristol Myers Squibb, MSD, Pfizer, Sanofi, Ipsen; Research grant/Funding (institution), Clinical Trial: Roche, Bristol Myers squibb, Astra-Zeneca, MSD, Pfizer, Seattle Genetics, Astellas, Janssen, Clouis, Incyte, Sanofi; Research grant/Funding (institution), Research Grant: MSD, Sanofi, Janssen. A.O. Siefker-Radtke: Advisory/Consultancy: Merck Bavarian Nordic Seattle Genetics Genentech Janssen Mirati AstraZeneca Nektar Therapeutics Pfizer; Speaker Bureau/Expert testimony: Janssen. A. Necchi: Advisory/Consultancy: Merck, AstraZeneca, Janssen, Incyte, Roche, Rainier Therapeutics, Clovis Oncology, Bayer, and Astellas/Seattle Genetics, Ferring, Immunomedics; Research grant/Funding (institution): Merck, Ipsen, and AstraZeneca; Honoraria (self): Roche, Merck, AstraZeneca, and Janssen. V. Naini: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. A. Santiago-Walker: Shareholder/Stockholder/Stock options, Full/Part-time employment: Janssen. A. Galluzzi: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. M. Monga: Full/Part-time employment: Janssen. E.F. Burgess: Shareholder/Stockholder/Stock options: Gilead Sciences, Exelixis, Clovis Oncology, Calithera Biosciences; Honoraria (self): Bayer, Exelixis. All other authors have declared no conflicts of interest.