"These results suggest that infigratinib has activity in patients with advanced urothelial carcinoma, regardless of the line of treatment,” says lead study author Dr. Yung Lyou.
Results of a retrospective analysis presented at the 2020 ASCO Virtual Scientific Program show that infigratinib demonstrates clinical activity in patients with metastatic urothelial carcinoma, regardless of what line the treatment was administered.
"Our data suggests similar activity of infigratinib in patients receiving it in the first-line setting versus subsequent lines for advanced urothelial carcinoma," lead study author Dr. Yung Lyou, an assistant clinical professor in the Department of Medical Oncology and Therapeutics Research at City of Hope, said in a pre-recorded presentation. "These results suggest that infigratinib has activity in patients with advanced urothelial carcinoma, regardless of the line of treatment."
Advanced urothelial carcinoma, Lyou noted, continues to be an incurable disease for many patients. Currently, immune checkpoint inhibitors and platinum-based chemotherapy serve as the foundation for treatment. However, only approximately 15% to 40% of patients respond to checkpoint inhibitors. Additionally, an estimated 20% of patients who have lower tract disease, and 40% to 75% who have upper tract disease, have fibroblast growth factor receptor 3 (FGFR3) mutations.
Infigratinib — a potent, oral FGFR1/2/3 inhibitor — has previously been shown to demonstrate significant clinical activity in patients with advanced urothelial carcinoma whose tumors harbor an FGFR3 mutation. To determine if there were any differences regarding the activity of infigratinib based on the number of previous lines of therapy a patient may have received, investigators assessed the outcomes of 67 patients (68.7% male) with advanced or metastatic urothelial cancer that harbored FGFR3 mutations.
To be eligible for enrollment, patients must have progressed on, or were intolerant to, platinum-based chemotherapy, unless contraindicated. Patients also had to undergo baseline imaging, including a CT of the chest, abdomen, and pelvis, as well as brain MRI or CT and technetium bone scan. Follow-up serial imaging comprised the same baseline CT imaging, along with bone scan if indicated, at eight-week intervals thereafter.
The main outcome of the study was to assess if there were any differences in objective response rates — the proportion of patients who had a complete or partial response to treatment — in patients who received infigratinib in the front-line setting (13) vs. those who received study drug in a later setting (54). Additional outcomes included a comparison of disease control rate (DCR), progression-free survival (PFS), overall response, overall survival (OS) and safety.
Patients within the trial were treated with oral infigratinib at 125 milligrams (mg) once a day on days one to 21 every 28 days until the disease progressed or an unacceptable toxicity was reached. A dose reduction to 100 mg followed by 75 mg a day was permitted, as well as further reductions on an individual basis.
Patients who received infigratinib in the first line achieved an overall objective response (ORR) rate of 30.8%, and patients who received study drug as a second- or later-line treatment had an ORR of 24.1%.
In a response assessment, there was one complete response among the overall patient population, which occurred in the group who received treatment outside of first line. There were four partial responses in the front-line setting and 12 in the later-line arm.
The best overall response in the front-line setting was 38.5% compared to 42.6% in the later-line setting. Patients within the front-line arm achieved a disease control rate of 46.2%, and patients who received the study drug after the first line achieved a disease control rate of 68.5%.
Among the overall population, the median PFS — amount of time from the start of treatment until disease progression — was similar between the first-line treatment arm (3.65 months) and the second- or later-line group (3.75 months). There was also no statistically significant difference in median OS between the front-line treatment arm (7.93 months) and the second- or later-line treatment arm (7.75 months).
Side effects considered severe and serious occurred in 98.5% of the patients within the first-line treatment arm and 68.7% of the patients in the other arm.
The researchers acknowledged that there were some limitations to the study, which included a relatively small sample of patients who received study drug in the first line.
The investigators did note in the presentation that the study had limitations, such as that a relatively small proportion of patients received infigratinib in the first-line setting, and that the current data also reflect an unplanned subset analysis.
“Collectively, these (data) support our ongoing adjuvant PROOF 302 study comparing infigratinib versus placebo in patients with resected disease to see if infigratinib would be beneficial in an even earlier line setting,” Lyou concluded.
A version of this story originally appeared on OncLive® as "Infigratinib Demonstrates Clinical Activity Across Settings in Urothelial Cancer."