medwireNews: The pan-FGFR inhibitor erdafitinib could be a treatment option for previously treated patients with locally advanced or metastatic urothelial carcinoma harboring FGFR aberrations, suggest phase II trial results.
In the BLC2001 study, the investigator-assessed objective response rate (ORR) was 40% for the 99 participants who received erdafitinib at a starting dose of 8 mg/day after progressing on at least one prior course of systemic chemotherapy. The lower bound of the confidence interval was more than 25%, which meant that the trial met its primary endpoint, say the researchers.
Three percent of the responses were complete, 37% were partial, and a further 39% of patients had stable disease, with a third remaining stable for more than 6 months, according to the article published in The New England Journal of Medicine.
Interestingly, the ORR was higher for the 74 individuals carrying FGFR mutations than for the 25 with FGFR fusions, at 49% and 16%, respectively.
Nevertheless, investigator Arlene Siefker-Radtke (The University of Texas MD Anderson Cancer Center, Houston, USA) and collaborators note that responses to the FGFR1–4 inhibitor were observed “regardless of previous chemotherapy, the number of previous courses of treatment, the presence of visceral metastasis, or baseline characteristics such as age, sex, hemoglobin level, or renal function.”
They also highlight the favorability of the ORR compared with trials of other FGFR inhibitors (ORRs, 0–25%), immune checkpoint inhibitors (13–21%), antibody–drug conjugates such as enfortumab vedotin or sacituzumab govitecan (33–34%), and historic chemotherapy data (approximately 10%) in this patient population.
Over a median follow-up of 11.0 months, the median progression-free and overall survival times were 5.5 and 13.8 months, respectively, with corresponding 12-month rates of 19% and 55%.
Adverse events (AEs) of grade 3 or 4 were reported by 67% of trial participants, with 46% considered related to the study drug. Hyponatremia was the most frequent AE of grade 3 or worse, occurring at a rate of 11%, followed by stomatitis and asthenia, at 10% and 7%, respectively.
Of note, the trial protocol allowed the dose of erdafitinib to be escalated to 9 mg/day for participants who did not reach the target serum phosphate level of 5.5 mg/dL. However, the incidence of grade 3 or worse AEs in this subgroup was comparable to that for the overall trial cohort, at 68% and 67%, respectively.
Erdafitinib has been approved in the USA on the basis of these results for the second- or later-line treatment of locally advanced or metastatic disease in patients with FGFR alterations.
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