THOR: trial | Bending the Curve: Trial by Trial

THOR

Erdafitinib compared with vinflunine or docetaxel or pembrolizumab in advanced urothelial cancer with selected FGFR alterations (THOR)

Phase 3NCT03390504

Population

Metastatic or unresectable urothelial carcinoma with select FGFR alterations and disease progression after prior treatment

Design

Global randomised open-label phase 3 trial in metastatic urothelial carcinoma with susceptible FGFR3/2 alterations. Cohort 1 (progression after one or two previous treatments that included an anti-PD-1 or anti-PD-L1): 1:1 erdafitinib or investigator's choice of docetaxel or vinflunine. Cohort 2 (anti-PD-(L)1-naive, progression on one prior treatment): 1:1 erdafitinib 8 mg once daily with guided escalation to 9 mg, or pembrolizumab 200 mg every 3 weeks. Primary endpoint overall survival.

Primary endpoint

Arms

Cohort 1: erdafitinib (experimental, n = 136): Erdafitinib
Cohort 1: chemotherapy (control, n = 130): Investigator's choice of docetaxel or vinflunine
Cohort 2: erdafitinib (experimental, n = 175): Erdafitinib 8 mg once daily with pharmacodynamically guided escalation to 9 mg
Cohort 2: pembrolizumab (control, n = 176): Pembrolizumab 200 mg every 3 weeks

People

Loriot Y, THOR Cohort 1 Investigators

OSHR 0.64 (95% CI 0.47–0.88)Δ median OS+4.3 monthsPFSHR 0.58 (95% CI 0.44–0.78)Δ median PFS+2.9 monthsOSHR 1.18 (95% CI 0.92–1.51)Δ median OS−0.2 months

Show the numbers

Results reported for THOR
Endpoint	Analysis	Cohort 1: erdafitinib / Cohort 2: erdafitinib	Cohort 1: chemotherapy / Cohort 2: pembrolizumab	Effect
OSCohort 1, after anti-PD-1/PD-L1 (n = 266)	primarymedian follow-up 15.9 monthsLoriot 2023	median 12.1 months	median 7.8 months	HR 0.64 (95% CI 0.47–0.88)P=0.005
PFSCohort 1, after anti-PD-1/PD-L1 (n = 266)	primarymedian follow-up 15.9 monthsLoriot 2023	median 5.6 months	median 2.7 months	HR 0.58 (95% CI 0.44–0.78)P<0.001
OSCohort 2, anti-PD-(L)1-naive (n = 351)	primarymedian follow-up 33 monthsSiefker-Radtke 2024	median 10.9 months	median 11.1 months	HR 1.18 (95% CI 0.92–1.51)P=0.18No statistically significant difference in OS.
PFSCohort 2, anti-PD-(L)1-naive (n = 351)	primarymedian follow-up 33 monthsSiefker-Radtke 2024	median 4.4 months	median 2.7 months	HR 0.88 (95% CI 0.7–1.1)
ORRCohort 2, anti-PD-(L)1-naive (n = 351)	primarymedian follow-up 33 monthsSiefker-Radtke 2024	40%	21.6%	Relative risk 1.85 (95% CI 1.32 to 2.59); not a hazard ratio.
DORCohort 2 responders	primarymedian follow-up 33 monthsSiefker-Radtke 2024	median 4.3 months	median 14.4 months	—

Results reported for THOR
Endpoint	Analysis	Cohort 1: erdafitinib / Cohort 2: erdafitinib	Cohort 1: chemotherapy / Cohort 2: pembrolizumab	Effect
OSCohort 1, after anti-PD-1/PD-L1 (n = 266)	primarymedian follow-up 15.9 monthsLoriot 2023	median 12.1 months	median 7.8 months	HR 0.64 (95% CI 0.47–0.88)P=0.005
PFSCohort 1, after anti-PD-1/PD-L1 (n = 266)	primarymedian follow-up 15.9 monthsLoriot 2023	median 5.6 months	median 2.7 months	HR 0.58 (95% CI 0.44–0.78)P<0.001
OSCohort 2, anti-PD-(L)1-naive (n = 351)	primarymedian follow-up 33 monthsSiefker-Radtke 2024	median 10.9 months	median 11.1 months	HR 1.18 (95% CI 0.92–1.51)P=0.18No statistically significant difference in OS.
PFSCohort 2, anti-PD-(L)1-naive (n = 351)	primarymedian follow-up 33 monthsSiefker-Radtke 2024	median 4.4 months	median 2.7 months	HR 0.88 (95% CI 0.7–1.1)
ORRCohort 2, anti-PD-(L)1-naive (n = 351)	primarymedian follow-up 33 monthsSiefker-Radtke 2024	40%	21.6%	Relative risk 1.85 (95% CI 1.32 to 2.59); not a hazard ratio.
DORCohort 2 responders	primarymedian follow-up 33 monthsSiefker-Radtke 2024	median 4.3 months	median 14.4 months	—

Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.

Data table

Endpoint	HR	95% CI
OS	0.64	0.47–0.88
PFS	0.58	0.44–0.78
OS	1.18	0.92–1.51
PFS	0.88	0.7–1.1

Illustrative — modelled from reported values, not trial data. OS, primary.

Show curves

Cohort 1: erdafitinib (experimental)
Cohort 1: chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Cohort 1: erdafitinib	Cohort 1: chemotherapy
0	100.0%	100.0%
8	63.2%	49.1%
15	42.3%	26.4%
23	26.8%	13.0%
30	17.9%	7.0%

Illustrative — modelled from reported values, not trial data. PFS, primary.

Show curves

Cohort 1: erdafitinib (experimental)
Cohort 1: chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)

Months	Cohort 1: erdafitinib	Cohort 1: chemotherapy
0	100.0%	100.0%
4	61.0%	35.8%
7	42.0%	16.6%
11	25.6%	5.9%
14	17.7%	2.7%

Appears in

2019 Erdafitinib for FGFR-altered urothelial cancer: BLC2001 to THOR

Sources

Loriot Y, Matsubara N, Park SH, Huddart RA, Burgess EF, Houede N, et al. Erdafitinib or Chemotherapy in Advanced or Metastatic Urothelial Carcinoma. N Engl J Med. 2023;389(21):1961-1971.
PubMed DOI
Siefker-Radtke AO, Matsubara N, Park SH, Huddart RA, Burgess EF, Özgüroğlu M, et al. Erdafitinib versus pembrolizumab in pretreated patients with advanced or metastatic urothelial cancer with select FGFR alterations: cohort 2 of the randomized phase III THOR trial. Ann Oncol. 2024;35(1):107-117.
PubMed DOI