LBA102 - THOR-2 cohort 1: Results of erdafitinib (ERDA) vs intravesical chemotherapy (chemo) in patients (pts) with high-risk non–muscle-invasive bladder cancer (HR NMIBC) with select fibroblast growth factor receptor alterations (FGFRALT) who received prior bacillus calmette-guérin (BCG) treatment

Background

Treatment (tx) options are limited for pts with HR NMIBC who have recurrence after BCG tx and are ineligible for/refuse radical cystectomy (RC). Erda, an oral selective pan-FGFR tyrosine kinase inhibitor, demonstrated an overall survival benefit over chemo in the phase 3 THOR study in pts with locally advanced/metastatic urothelial carcinoma with FGFRalt. We report the first randomized data in pts with recurrent, BCG-treated HR NMIBC with FGFRalt from Cohort 1 of THOR-2 (NCT04172675).

Methods

Adult pts with recurrent, BCG-treated, papillary-only HR NMIBC (high-grade Ta/T1) and select FGFRalt refusing/ineligible for RC were randomized 2:1 to 6 mg oral erda or investigator’s choice of intravesical chemo (mitomycin C or gemcitabine). Primary end point: recurrence-free survival (RFS). Secondary end points: RFS rate at 6 and 12 mo and safety.

Results

73 pts (median age: 69 y) were randomized to erda (n=49) and chemo (n=24). Study enrollment was discontinued because of slow accrual. Median follow-up was 13.4 mo for both groups. Median RFS was not reached for erda and was 11.6 mo for chemo, with an estimated hazard ratio of 0.28 (Table). 6- and 12-mo RFS rate was 96% and 77% for erda vs 73% and 41% for chemo, respectively. Grade (Gr) 3-4 tx-related adverse events (TRAEs) occurred in 15 (31%) and 1 (4%) pts with erda and chemo, respectively; 14 (29%) and 0 pts had TRAEs leading to discontinuation of erda and chemo, respectively. Central serous retinopathy occurred in 19 pts (39%) with erda (Gr 1-2, 17 pts) and resolved in 11 pts (58%). Table: LBA102

^aCensoring: 1) Recurrence-free + alive or unknown status, censored at last assessment; 2) no post-baseline assessment, censored at randomization; 3) withdrew consent or lost to follow-up prior to RFS event, censored at last assessment; 4) start subsequent anticancer tx prior to RFS event, censored at last assessment before new tx start. ^bEstimated using stratified Cox proportional hazards regression model. Hazard ratio <1 indicates longer RFS in erda vs chemo. ^cBased on an unstratified log-rank test.

Conclusions

Erda prolonged RFS compared with chemo in pts with papillary-only HR NMIBC with FGFRalt who had recurrence after BCG tx. Erda toxicity was generally consistent with the known safety profile of oral FGFR inhibitors.

Clinical trial identification

NCT04172675.

Editorial acknowledgement

Editorial support was provided by Benjamin Ricca, PhD, of Parexel and funded by Janssen Global Services, LLC.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

J.W.F. Catto: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca/MedImmune, Janssen, Ferring, Roche; Financial Interests, Personal, Speaker’s Bureau: ASCO, Roche, StraZeneca/MedImmune, MSD oncology, Nucleix; Financial Interests, Personal, Other, Travel, Accommodations, expenses: European Association of Urology; Financial Interests, Personal, Other, Honoraria: Abbot Laboratories; Financial Interests, Personal, Research Funding: Roche/Genentech. B. Tran: Financial Interests, Personal, Speaker, Consultant, Advisor: Amgen, Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Ipsen, IQVIA, Janssen-Cilag, MSD Oncology, Novartis, Pfizer/EMD Serono, Roche Molecular Diagnostics, Sanofi, Tolmar; Financial Interests, Personal, Other, Honoraria: Amgen, Astellas Pharma, Bayer, Bristol Myers Squibb, Janssen, Janssen-Cilag, Sanofi, Tolmar, Pfizer; Financial Interests, Institutional, Research Funding: Amgen, Astellas, AstraZeneca, Bayer Pharma, Genentech, Janssen-Cilag, Pfizer; Financial Interests, Personal, Research Funding: from Bristol Myers Squibb, Ipsen, Merck Sharp & Dohme. M. Roupret: Financial Interests, Personal, Speaker, Consultant, Advisor: Lilly, GSK, Ipsen, Astellas, Takeda, Sanofi Pasteur, Medac, Ferring, Janssen-Cilag; Financial Interests, Personal, Research Funding: GSK, Pfizer, Roche; Financial Interests, Personal, Other, Honoraria: Roche, Zambon, Janssen, Astellas, Ipsen Pharma, Bayer S.A.S; Financial Interests, Personal, Advisory Board, Study Participation: Pfizer, Roche. Y. Loriot: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Immunomedics, Janssen, Loxo/Lilly, Pfizer/EMD Serono, Roche, and Taiho Pharmaceutical; Financial Interests, Institutional, Speaker, Consultant, Advisor: MSD Oncology, Janssen; Financial Interests, Personal, Other, Travel Reimbursment: Astellas, AstraZeneca, Janssen Oncology, MSD Oncology, Roche; Financial Interests, Personal, Research Funding: Astellas Pharma, AstraZeneca, Basilea, Bristol Myers Squibb, Exelixis, Gilead Sciences, Incyte, Janssen Oncology, Merck KGaA, MSD Oncology, Nektar, Pfizer, Roche, Sanofi, and Taiho Pharmaceutical. H. Nishiyama: Financial Interests, Personal, Speaker, Consultant, Advisor: MSD, Chugai Pharma, Bayer Yakuhin, Janssen, and Lilly; Financial Interests, Personal, Other, Honoraria: MSD, Chugai Pharma, and Astellas Pharma; Financial Interests, Institutional, Research Funding: Astellas Pharma, Ono Pharmaceutical, Takeda, and Bayer Yakuhin. J. Palou: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas, Janssen, Merck, Ferring, AstraZeneca, Sandoz, and Novartis. S. Daneshmand: Financial Interests, Personal, Speaker, Consultant, Advisor: Photocure, Taris, Ferring, and QED Therapeutics; Financial Interests, Personal, Other, Honoraria: Photocure, QED Therapeutics, Olympus, Ferring, Pacific Edge, Johnson & Johnson, Aduro Biotech, Janssen, Bristol Myers Squibb, and Allergan; Financial Interests, Personal, Other, research funding and reimbursement for travel, accommodations, or expenses: Photocure; Financial Interests, Personal, Stocks or ownership: Taris. S.A. Hussain: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Merck, Roche, Bristol Myers Squibb, and Janssen; Financial Interests, Personal, Other, Personal Fees and Grants: Boehringer Ingelheim and Pierre Fabre. G. Procopio: Financial Interests, Personal, Speaker, Consultant, Advisor: Astellas Pharma, AstraZeneca, Bayer, Bristol Myers Squibb, Eisai, Ipsen, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, and Sanofi; Financial Interests, Personal, Research Grant: Astellas, Ipsen, and Novartis. V. Guadalupi: Financial Interests, Institutional, Research Funding: Ipsen and Janssen. V. Naini: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. L. Crow: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. S. Triantos: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. M. Baig: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks or ownership: Johnson & Johnson. G.D. Steinberg: Financial Interests, Personal, Speaker, Consultant, Advisor: AbbVie, Aduro, Astellas, AstraZeneca, BioCanCell, Boston Scientific, Bristol Myers Squibb, CG Oncology, Ciclomed, Combat Medical, Dendreon, EnGene Bio, Epivax Therapeutics, Fergene, Ferring, Fidia Farmaceuticals, FKD, Heat Biologics, Ipsen, Janssen, MDxHe; Financial Interests, Personal, Other, clinical trial protocol committee member: Bristol Myers Squibb, CG Oncology, Fidia, Janssen, Merck, Pfizer, PhotoCure, Protara, and Seagen; Financial Interests, Personal, Other, Equity Stock: Epivax Therapeutics and Urogen. All other authors have declared no conflicts of interest.