2362MO - Erdafitinib (erda) vs chemotherapy (chemo) in patients (pts) with advanced or metastatic urothelial cancer (mUC) with select FGFR alterations (FGFRalt): Subgroups from the phase III THOR study

Background

FGFRalt are seen in ∼20% of pts with mUC. Erda is an oral pan-FGFR tyrosine kinase inhibitor for pts with locally advanced or mUC with susceptible FGFR3/2alt who have progressed after platinum-containing chemo. THOR (NCT03390504), a randomized phase 3 study, assessed whether erda provided an overall survival (OS) advantage vs chemo in pts with mUC who progressed after 1-2 prior therapies (tx), including anti-PD-(L)1.

Methods

Pts (≥18 y) with unresectable advanced/mUC and select FGFR3/2alt (mutations/fusions), ECOG PS 0-2, adequate organ function, progression on/after 1-2 prior lines of systemic tx that included anti-PD-(L)1 were randomized 1:1 to erda (8 mg with pharmacodynamically guided uptitration to 9 mg) QD or investigator’s choice of chemo (docetaxel or vinflunine) Q3W until disease progression or intolerable toxicity. Primary end point was OS. Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.

Results

266 pts were randomized (median [m] age 67 y, follow-up 16 mo) to erda (N=136) or chemo (N=130). Primary end point was met: mOS 12.1 vs 7.8 mo in erda vs chemo (HR=0.64; 95% CI, 0.47-0.88). OS benefit was seen across subgroups (Table). Erda improved mPFS (6 vs 3 mo) and ORR (46% vs 12%) vs chemo. Most frequent tx-related adverse events (TRAEs): hyperphosphatemia (79%), diarrhea (55%), and stomatitis (46%) with erda; anemia (28%), alopecia (21%), and nausea (20%) with chemo. 46% in each arm had Gr 3/4 TRAEs. 1 and 6 pts had TRAEs leading to death with erda and chemo, respectively. Table: 2362MO

^aChemo group tx.

Conclusions

In pts with FGFRalt advanced/mUC after prior anti-PD-(L)1 tx, erda significantly improved OS vs chemo. Clinically relevant subgroups showed a consistent OS benefit for erda. No new safety signals were observed. These results support the role of erda to treat pts with FGFRalt mUC after anti-PD-(L)1 tx.

Clinical trial identification

NCT03390504.

Editorial acknowledgement

Medical writing assistance was provided by Benjamin Ricca, PhD, of Parexel, and was funded by Janssen Global Services, Llc.

Legal entity responsible for the study

Janssen Research & Development.

Funding

Janssen Research & Development.

Disclosure

Y. Loriot: Financial Interests, Personal, Advisory Board: Merck Kga, Pfizer, Gilead, seattle genetics, Taiho; Financial Interests, Personal, Other, lectures, advisory boards: MSD, AstraZeneca, Astellas, Janssen; Financial Interests, Personal, Other, lectures, advisroy boards: Roche, BMS; Financial Interests, Institutional, Research Grant: Janssen, Sanofi, MSD, Roche, celsius; Financial Interests, Institutional, Steering Committee Member: Janssen; Financial Interests, Steering Committee Member: MSD, Astellas, Gilead/Immunomedics, Taiho; Financial Interests, Personal, Steering Committee Member: Basilea; Financial Interests, Institutional, Local PI: Pfizer, MSD, Janssen, Exelexis, AstraZeneca, Pfizer, Merck Kga, BMS, Astellas, Gilead, Incyte; Financial Interests, Institutional, Coordinating PI: Janssen; Non-Financial Interests, Member: ESMO, ASCO, AACR; Non-Financial Interests, Other, scientific committee: ARC. N. Matsubara: Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy: Janssen, MSD, Eli Lilly; Financial Interests, Institutional, Research Funding: Janssen, AstraZeneca, Bayer, MSD, Taiho, Astellas, Amgen, Eisai, Eli Lilly, Takeda, Pfizer, Seagen, Chugai, AbbVie, Novartis. R.A. Huddart: Financial Interests, Personal, Other, Personal Fees: Aspen Parkside Hospital; Financial Interests, Personal, Speaker, Consultant, Advisor, Consultancy Fees: Bristol Myers Squibb, Roche, Merck Sharp & Dohme, Janssen Oncology, Nektar, and Bayer; Financial Interests, Personal, Other, Honoraria: Janssen Oncology; Financial Interests, Personal, Other, Travel: Janssen Oncology, Roche/Genentech, MSD Oncology, and Nektar; Financial Interests, Personal, Other: Merck Sharp & Dohme, Roche, Bristol Myers Squibb, and Janssen; Financial Interests, Personal, Other, Patents: Janssen; Financial Interests, Personal, Leadership Role: Cancer Clinic London Limited Liability Partnership. N. Houede: Financial Interests, Personal, Other, Consultancy Fees: Astellas Pharma, AstraZeneca, Bristol Myers Squibb, Janssen, MSD/Merck. B. Laguerre: Financial Interests, Personal, Other, ASCO GU symposium 2023 (travel and registration): Pfizer; Financial Interests, Personal, Other, honoraria: Astellas, Janssen, Pfizer; Financial Interests, Personal, Other, registration ASCO virtual meeting 2022: BMS; Financial Interests, Personal, Other, registration ASCO GU symposium 2022 (virtual): MSD. V. Guadalupi: Financial Interests, Institutional, Research Funding: Ipsen. S. Triantos, S. Akapame, K. Deprince, S. Mukhopadhyay: Financial Interests, Personal, Other, Employment: Janssen; Financial Interests, Personal, Stocks/Shares: Janssen. A.O. Siefker-Radtke: Financial Interests, Personal, Other, Consulting/advisory fees: AstraZeneca; Financial Interests, Personal, Other, Consulting/advisory honorarium: Bavarian Nordic, Bristol Myers Squibb, Genentech, Gilead, Ideeya Biosciences, Immunomedics, Janssen, Loxo, Merck, Mirati, Nektar Therapeutics, Seattle Genetics, Taiho; Financial Interests, Institutional, Local PI, Clinical research trial: Basilea Pharmaceutica, Bristol Myers Squibb; Financial Interests, Institutional, Local PI, Clinical research trial: Janssen, Merck, Millennium, Nektar. All other authors have declared no conflicts of interest.