Erdafitinib improves outcomes vs. chemotherapy in advanced FGFR-altered urothelial cancer
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Key takeaways:
- Median OS favored patients treated with erdafitinib over chemotherapy (12.1 months vs. 7.8 months).
- Patients had a median PFS of 5.6 months with erdafitinib vs. 2.7 months with chemotherapy.
CHICAGO — Erdafitinib improved OS, PFS and objective response rate compared with chemotherapy among patients with advanced or metastatic urothelial cancer with select fibroblast growth factor receptor alterations.
Results of the phase 3 THOR trial, presented at ASCO Annual Meeting 2023, showed the FGFR inhibitor reduced the risk for death by 36% among the patient population compared with investigator’s choice of chemotherapy, according to researchers.
“The phase 3 THOR study supports the clinical efficacy of erdafitinib as the standard-of-care option for patients with metastatic urothelial carcinoma with FGFR alterations after anti-PD-(L)1 treatment,” Yohann Loriot, MD, PhD, director of the bladder cancer program at Gustave Roussy in Villejuif, France, said during a presentation. “The overall survival benefit of erdafitinib in these patients support molecular testing for FGFR alterations in all patients with metastatic urothelial carcinoma.”
Background and methodology
An umet need exists for treatments after checkpoint inhibitor therapy for patients with metastatic urothelial carcinoma, Loriot said.
Erdafitinib (Balversa; Janssen Oncology), an oral, selective pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, received FDA accelerated approval to treat locally advanced or metastatic urothelial cancer in adults with FGFR3/2 alterations who have progressed following platinum-containing chemotherapy.
The randomized, phase 3 THOR trial evaluated the efficacy and safety of the agent vs. investigator’s choice of chemotherapy (docetaxel or vinflunine) among patients with advanced or metastatic urothelial cancer who progressed after one or two prior treatments, including an anti-PD-L1 agent.
Researchers randomly assigned 266 eligible patients (median age, 67 years) with unresectable advanced or metastatic urothelial cancer and select FGFR3/2 alterations to receive either 8 mg erdafitinib once a day with pharmacodynamically guided uptitration to 9 mg on day 14 (n = 136) or investigator’s choice of chemotherapy (n = 130) until disease progression of intolerable toxicity.
Among the study participants, 30% had received one prior line of systemic therapy, 70% had received two prior lines of systemic therapy, 74% had visceral metastases and 90% were PD-L1 low. All had received anti-PD-1 therapy in the first- or second-line setting.
OS served as the primary endpoint, with PFS, ORR and safety as secondary endpoints.
Median follow-up was 15.9 months.
Results
Researchers reported a median OS of 12.1 months for patients treated with erdafitinib and 7.8 months for patients in the chemotherapy population (HR = 0.64; 95% CI, 0.47-0.88).
The erdafitinib group also had longer median PFS (5.6 months vs. 2.7 months; HR = 0.58; 95% CI, 0.44-0.78) and a higher ORR (45.6% vs. 11.5%).
No new safety signals occurred during the trial.
Serious treatment-related adverse events occurred among 13.3% of patients treated with erdafitinib and 24% of patients treated with chemotherapy, with 46% of patients in each group reporting grade 3/grade 4 treatment-related adverse events. These included PPE syndrome (9.6%), stomatitis (8.1%) and hyperphosphatemia (5.2%) in the erdafitinib group and neutropenia (13.4%) febrile neutropenia (8.9%) and leukopenia (8%) in the chemotherapy group. Central serous retinopathy occurred in 23 patients (17%) in the erdafitinib group.
Treatment-related adverse events that led to dose reductions occurred more often in the erdafitinib group (66%) than the chemotherapy group (21%). A total of 8% of erdafitinib patients and 13% of chemotherapy patients discontinued treatment due to treatment-related adverse events.
One patient in the investigative group and six in the chemotherapy group died due to a treatment-related adverse event.
Perspective
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Daniel P. Petrylak, MD
All patients with metastatic urothelial carcinoma should be tested for FGFR3/2 alterations, preferably at first diagnosis.
The THOR study demonstrates superior overall survival, PFS and objective response rates of erdafitinib compared to single-agent chemotherapy in patients with FGFR3/2 alterations. Future studies are needed to develop rational sequencing of erdafitinib, enfortumab vedotin (Padcev, Astellas, Seagen) and sacituzumab govitecan (Trodelvy, Gilead). Right now, I think the only way you can select is based upon toxicity.
Understanding the resistance pathways is essential to developing effective combination therapy, either with immune checkpoints, tyrosine kinase inhibitors and, as we’ve found in our laboratory at Yale, HDAC inhibitors.
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Loriot Y, et al. Abstract LBA4619. Presented at: ASCO Annual Meeting 2023; June 2-6, 2023; Chicago.
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