Clinical trialPhase 3Bladder cancer

Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma

N Engl J Med · 2023266 patients (136 erdafitinib, 130 chemotherapy)

Loriot Y, Matsubara N, Park SH, et al. N Engl J Med. 2023. 389:1961-1971

Study type: Clinical trial
Study name: THOR
Phase: Phase 3
Design: Randomised, open-label, global trial (cohort 1; 1:1 randomisation)
Sample size: 266 patients (136 erdafitinib, 130 chemotherapy)
Source: N Engl J Med · 2023
Trial registration: NCT03390504

In plain words

In some advanced bladder cancers, there is a change in a gene called FGFR3, which can be found by genetic testing of the tumour (on tissue). Erdafitinib is a tablet that targets this pathway. In the THOR study, in patients whose disease had grown after immunotherapy, this tablet increased median survival from about 8 months to 12 months compared with chemotherapy given into a vein. Severe side effects were about as common in both groups, but the types of side effects differ, and blood phosphate checks and eye examinations are needed.

Key results

12.1 vs 7.8 months

Median overall survival

HR for death 0.64 (95% CI 0.47 to 0.88); P=0.005; median follow-up 15.9 months

5.6 vs 2.7 months

Median progression-free survival

HR 0.58 (95% CI 0.44 to 0.78); P<0.001

45.9% vs 46.4%

Grade 3 or 4 treatment-related adverse events

0.7% vs 5.4%

Treatment-related death

Drugs in this study:Docetaxel (Taxotere)

Dose and schedule cards

Erdafitinib (THOR)

Susceptible FGFR3 alterations (approved companion diagnostic) after at least one line of systemic therapy; in THOR, after a PD-1/PD-L1 inhibitor; ECOG 0 to 2Cycle length: ContinuousOn the page “Bladder cancer” · Advanced or metastatic disease: after first line

Susceptible FGFR3 alterations (approved companion diagnostic) after at least one line of systemic therapy; in THOR, after a PD-1/PD-L1 inhibitor; ECOG 0 to 2

Drug	Dose	Route	Schedule
Erdafitinib	8 mg once daily; increase to 9 mg on Days 14 to 21 if serum phosphate is less than 9.0 mg/dL	Oral, with or without food; swallow whole	Daily, continuous

Cycle length: Continuous
Duration: Until progression or unacceptable toxicity

Per the FDA label and the trial. Increase the dose to 9 mg only in the absence of ocular adverse reactions or grade 2 or higher adverse reactions; monitor phosphate monthly. Ophthalmologic examination monthly during the first 4 months, then every 3 months, and urgently for any visual symptom (serous retinal detachment). Dose reductions: 9, 8, 6, 5 and 4 mg.

On the page “Bladder cancer” · Advanced or metastatic disease: after first line

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Erdafitinib

Oral erdafitinib at a starting dose of 8 mg once daily continuously (21-day cycles), increased to 9 mg based on serum phosphate, until progression or unacceptable toxicity. Per the FDA label: measure serum phosphate 14 to 21 days after starting, and if it is below 9.0 mg/dL with no eye toxicity or grade 2 or higher adverse event, increase the dose to 9 mg; ophthalmological examination monthly for the first 4 months, then every 3 months.

2Chemotherapy of physician's choice

Docetaxel 75 mg/m² IV (1-hour infusion) every 3 weeks, or vinflunine 320 mg/m² IV (20-minute infusion) every 3 weeks, until disease progression or unacceptable toxicity.

Source of the regimen details: ClinicalTrials.gov NCT03390504 and the FDA label for BALVERSA (DailyMed)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

266 patients with metastatic or unresectable urothelial carcinoma (predominantly transitional histology) with susceptible FGFR3 or FGFR2 alterations (central molecular testing) who had progressed after 1 or 2 prior lines of systemic therapy including a PD-1/PD-L1 inhibitor (cohort 1); ECOG performance status 0 to 2 and adequate bone marrow, liver and kidney function.

Endpoints

Primary outcome: overall survival. Secondary outcomes: progression-free survival, objective response and safety.

Safety and side effects

The rate of grade 3 or 4 treatment-related adverse events was similar in the two groups (45.9% with erdafitinib and 46.4% with chemotherapy), but deaths due to treatment-related adverse events were fewer with erdafitinib (0.7% versus 5.4%). Adverse events specific to FGFR inhibitors, such as hyperphosphataemia and skin, nail and eye toxicities, need monitoring (details in the full text).

Clinical significance and place in guidelines

On 19 January 2024, based on cohort 1 of THOR, the FDA converted the accelerated approval of erdafitinib to full approval; indication: adults with locally advanced or metastatic urothelial carcinoma with susceptible FGFR3 genetic alterations (by an approved companion diagnostic) who have progressed after at least one prior line of systemic therapy. The 2025 EAU guideline recommends using susceptible FGFR3 alterations to select patients for erdafitinib (strong recommendation).

Limitations

Open-label design; the comparator was single-agent chemotherapy with limited efficacy; most patients were treated before wide access to enfortumab vedotin, and the exact place of erdafitinib in today's treatment sequence (after enfortumab vedotin + pembrolizumab) is unclear.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.