Abstract 750P
Background
We report on subgroup analyses of efficacy outcomes after median 2 years of treatment with ERDA in pts with mUC with susceptible FGFR3/2 alterations in the pivotal BLC2001 phase 2 trial (NCT02365597).
Methods
Duration of response (DoR), progression-free survival (PFS), and overall survival (OS) were assessed by FGFR alteration (mutations [m] and/or fusions [f] were analyzed as present [+] or absent [-]), primary tumor location (upper vs lower tract), presence of visceral metastases, prior chemotherapy (CT), and prior immunotherapy (IO) among 101 pts receiving the established ERDA dosage (8 mg/d continuous in 28-d cycles with uptitration to 9 mg/d if a protocol-defined target serum phosphate level was not reached and no treatment-related adverse events were observed).
Results
Median follow-up was 24 mos. Most pts (69%) were FGFRm+f-, 25% were FGFRm-f+, and 6% were FGFRm+f+. Median DoR was not impacted by FGFR alteration type (Table). Median PFS and OS, respectively, were 5.6 and 12.0 mos for FGFRm+f- pts and 2.8 and 10.3 mos for FGFRm-f+ pts. Most pts had primary tumors in the lower tract (75%); most (77%) had visceral metastases; DoR, PFS, and OS were similar regardless of primary tumor location or presence of visceral metastases (Table). Most pts (88%) had prior CT; median DoR, PFS, and OS were shorter for pts with prior CT vs those without prior CT (Table). 24% of pts had prior IO; DoR, PFS, and OS were similar regardless of prior IO. Table: 750P
| Outcomes in Subgroups of Patients in the BLC2001 Study | ||||
| Patients, n | Outcome, median, mo | |||
| DoR | PFS | OS | ||
| FGFR alteration | ||||
| FGFRm+f- | 70 | 6.0 | 5.6 | 12.0 |
| FGFRm-f+ | 25 | 6.2 | 2.8 | 10.3 |
| FGFRm+f+ | 6 | 5.6 | 6.9 | 15.0 |
| Tumor location | ||||
| Upper tract | 25 | 6.7 | 4.2 | 10.3 |
| Lower tract | 76 | 6.0 | 5.6 | 13.8 |
| Presence of visceral metastases | ||||
| Yes | 78 | 6.0 | 5.5 | 10.3 |
| No | 23 | 5.3 | 5.8 | 14.1 |
| Use of prior CT | ||||
| Prior CT | 89 | 5.6 | 5.5 | 10.6 |
| CT naive | 12 | 14.3 | 14.9 | 20.8 |
| Use of prior IO | ||||
| Prior IO | 24 | 6.5 | 5.7 | 10.9 |
| No prior IO | 77 | 5.6 | 5.5 | 12.0 |
Conclusions
Pts with locally advanced or metastatic UC derived benefit from ERDA regardless of FGFR alteration type, tumor location, presence of visceral metastases, or prior treatment with IO. Although the sample size was small, CT-naive pts exhibited clinically meaningful PFS and OS estimates.
Clinical trial identification
NCT02365597.
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. 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, AstraZeneca; Honoraria (self): Roche, Merck, AstraZeneca, Janssen. A.O. Siefker-Radtke: Advisory/Consultancy: Merck Bavarian Nordic Seattle Genetics Genentech Janssen Mirati AstraZeneca Nektar Therapeutics Pfizer; Speaker Bureau/Expert testimony: Janssen. 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, AstraZeneca, MSD, Pfizer, Seattle Genetics, Astellas, Janssen, Clouis, Incyte Sanofi; Research grant/Funding (institution), Research Grant: MSD, Sanofi, Janssen. J. Garcia-Donas: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol Myers Squibb; Research grant/Funding (self): Novartis; Honoraria (self), Research grant/Funding (self): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Honoraria (self): AstraZeneca, Janssen; Research grant/Funding (self): Astellas. R.A. Huddart: Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Janssen; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Honoraria (institution), Advisory/Consultancy, Research grant/Funding (institution): MSD; Honoraria (self), Advisory/Consultancy, Travel/Accommodation/Expenses: Nektar; Advisory/Consultancy: Bristol Myers Squibb; Advisory/Consultancy: Bayer; Shareholder/Stockholder/Stock options: Cancer Centre London. E.F. Burgess: Shareholder/Stockholder/Stock options: Gilead Sciences, Exelixis, Clovis Oncology, Calithera Biosciences ; Honoraria (self): Bayer, Exelixis. M.T. Fleming: Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen. A. Rezazadeh: Shareholder/Stockholder/Stock options: ECOM Medical; Advisory/Consultancy: AstraZeneca, Bayer, Pfizer, Novartis, Genentech, Bristol Myers SquibbEMD Serono; Speaker Bureau/Expert testimony: Janssen, Astellas Medivation, Pfizer, Novartis, Sanofi, 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, Bio Clin Therapeutics, Clovis Oncology, Bavarian Nordic, Seattle Genetics, Immunomedics, Epizy; Travel/Accommodation/Expenses: Genentech, Prometheus Laboratories, Astellas Medication, Janssen, Eisai, Bayer, Pfizer, Novartis, Exelixis, AstraZeneca. B. Mellado: Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Janssen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (self): Roche; Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Astellas; Advisory/Consultancy, Research grant/Funding (self): Bayer; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi. M. Joshi: Advisory/Consultancy, Travel/Accommodation/Expenses: Sanofi; Research grant/Funding (institution): Astra-Zeneca; Research grant/Funding (institution): Pfizer, Eisai; Advisory/Consultancy, Travel/Accommodation/Expenses: Bayer. I. Duran: Research grant/Funding (institution): AstraZeneca, Roche; Advisory/Consultancy, Officer/Board of Directors: Roche, BMS, MSD, Pharmacyclycs, Jansen, Ipsen, Novartis; Honoraria (self): Roche, BMS, MSD, Jansen, Ipsen, Novartis, Astellas; Travel/Accommodation/Expenses: Ipsen, AstraZeneca. Y. Zakharia: Advisory/Consultancy: Amgen, Roche Diagnostics, Novartis, Janssen, Eisai, Exelixis, Castle Bioscience, Array, Bayer, Pfizer, Clovis, EMD serono; Honoraria (self): Janssen; Research grant/Funding (institution): NewLink Genetics, Pfizer, Exelixis, Eisai, Janssen . M. Fu: Full/Part-time employment: Janssen; Shareholder/Stockholder/Stock options: Johnson & Johnson. A. Santiago-Walker: Shareholder/Stockholder/Stock options, Full/Part-time employment: Janssen. A. O'Hagan: Full/Part-time employment: Janssen Pharmaceuticals; Shareholder/Stockholder/Stock options: Johnson & Johnson. M. Monga: Full/Part-time employment: Janssen Pharmaceuticals. S.T. Tagawa: Research grant/Funding (institution): Sanofi, Medivation, Astellas, Janssen, Amgen, Progenics, Dendreon, Lilly, Genentech, Newlink, BMS, Inovio, AstraZeneca, Immunomedics, Aveo, Rexahn, Atlab, Boehringer Ingelheim, Millennium, Bayer, Merck, Abbvie, Karyopharm, Endocyte, Clovis, Seattle Geneti; Honoraria (self): Sanofi, Medivation/Astellas, Dendreon, Janssen, Genentech, Bayer, Endocyte, Eisai, Immunomedics, Karyopharm, Abbvie, Tolmar, Seattle Genetics, Amgen, Clovis, QED, Pfizer, AAA/Novartis, Genomic Health, POINT Pharma, Ambrx; Non-remunerated activity/ies: Atlab Pharma, Telix Pharma, Phosplatin Therapeutics, Amgen. All other authors have declared no conflicts of interest.