CHICAGO — Erdafitinib induced a robust response among patients with chemotherapy refractory metastatic or unresectable urothelial carcinoma and FGFR alterations, according to results of a primary analysis presented at the ASCO Annual Meeting.
“Patients with advanced urothelial carcinoma typically have poor clinical outcomes. Even with standard-of-care chemotherapy, evidence of objective response rates are around 10% or less with a median survival of 7 months to 9 months. It is clear that additional treatment options are necessary in order to benefit our patients,” Arlene O. Siefker-Radtke, MD, professor in the department of genitourinary medical oncology and the division of cancer medicine at The University of Texas MD Anderson Cancer Center, said during her presentation.
Erdafitinib (Janssen, Astex Therapeutics) — an investigational oral pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor — previously demonstrated positive activity among patients with metastatic unresectable urothelial carcinoma and other histologies, including cholangiocarcinoma. About 15% to 20% of patients with metastatic urothelial carcinoma harbor FGFR alterations.
For the current global, open-label, phase 2 study, researchers assessed the safety and efficacy of 8 mg erdafitinib daily in 99 patients (median age, 68 years) with metastatic or surgically unresectable urothelial carcinoma and FGFR alterations. Patients had experienced progression on at least one prior systemic chemotherapy or within 12 months of neoadjuvant chemotherapy, or they were chemotherapy naive and ineligible for cisplatin.
Overall response rate served as the primary outcome.
In the lead-in phase of the trial, researchers randomly assigned patients to a continuous 6 mg erdafitinib daily regimen or an intermittent schedule of 10 mg erdafitinib for 1 week on, 1 week off. On the basis of toxicity and early observed activity, researchers selected the continuous dosing schedule. Additional pharmacokinetic modeling led to an increase of the dose to 8 mg daily with uptitration to 9 mg among patients who did not experience toxicities.
According to study results, ORR was 40% (95% CI, 30.7-50.1) — which included three complete responses — and 76% of patients had a reduction in the sum of target lesion diameters.
Median PFS was 5.5 months (95% CI, 4.2-6) and median OS was 13.8 months (95% CI, 9.8-not estimable).
The most common treatment-related adverse events included hyperphosphatemia (73%), stomatitis (55%) and dry mouth (43%). Serious adverse events occurred in nine patients; there were no grade 4 or grade 5 events.
“Erdafitinib was well tolerated, with a safety profile that allows continuous dosing and uptitration to 9 mg daily. On the basis of these results, the FDA granted erdafitinib breakthrough therapy designation status in March,” Siefker-Radtke said.
The phase 3 THOR trial of erdafitinib vs. chemotherapy or pembrolizumab (Keytruda, Merck) in 630 patients with urothelial carcinoma is underway, and the phase 1b/2 NORSE trial of erdafitinib plus a PD-1 inhibitor also is underway for patients with urothelial carcinoma, according to Siefker-Radtke. – by Jennifer Southall
Seifker-Radtke, et al. Abstract 4503. Presented at: ASCO Annual Meeting; June 1-5, 2018; Chicago.
Disclosures: Seifker-Radtke reports consultant/advisory roles with Astrazeneca, Bristol-Myers Squibb, Eisai, EMD Serono, Genentech, Inovio Pharmaceuticals, Janssen, Lilly, Merck and NCCN; research funding from Bristol-Myers Squibb, Janssen, Michael and Sherry Sutton Fund for Urothelial Cancer, NIH and Takeda; and a speakers bureau role with Genentech. Please see the abstract for all other authors’ relevant financial disclosures.