Erdafitinib is efficacious in FGFR-altered urothelial carcinoma

Erdafitinib, an oral pan–fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, is efficacious when used to treat urothelial cancer harboring FGFR genetic alterations, although dose adjustments are commonly needed, suggests a multicenter phase 2 trial.

“Mutations and fusions in FGFR2/3 are common in patients with urothelial carcinoma, particularly in the luminal I subtype, and can cause constitutive FGFR signaling that may contribute to carcinogenesis,” write Yohann Loriot, MD, of Gustave Roussy, Université Paris-Sud and Université Paris-Saclay, in Villejuif, France, and coinvestigators. Up to 20% of patients with advanced disease and fully 37% of those with upper-tract tumors have alterations in these genes. “ Thus, FGFR inhibition may be particularly appropriate in patients with luminal I subtype disease, in which immunotherapeutic approaches may be less effective,” they noted.

In the trial, 99 patients with pretreated locally advanced and unresectable or metastatic urothelial carcinoma having FGFR alterations were given single-agent, open-label erdafitinib (Balversa) for a median of five cycles. The drug was recently granted accelerated approval by the Food and Drug Administration for this indication.

The rate of confirmed response according to investigator assessment was 40% (3% of patients had a complete response and 37% had a partial response), based on trial results reported in the New England Journal of Medicine. The response rate was 59% among the subset who had previously received immunotherapy.

With a median follow-up of 11.0 months, the median duration of progression-free survival was 5.5 months, and the median duration of overall survival was 13.8 months.

Fully 46% of patients experienced a grade 3 or higher treatment-related adverse event, most commonly hyponatremia (11%), stomatitis (10%), and asthenia (7%). Nearly 56% of the trial population as a whole required a dose reduction. However, only 13% of patients stopped treatment because of an adverse event, and there were no treatment-related deaths.

“This study met its primary objective,” Dr. Loriot and coinvestigators concluded. “These findings showed that among patients with locally advanced and unresectable or metastatic urothelial carcinoma with certain FGFR alterations, erdafitinib had promising antitumor activity.”

“The response to erdafitinib was rapid and independent of the number of previous courses and types of therapy, the presence of visceral metastasis, or tumor location,” they wrote. In addition, the efficacy appears to be better than that achieved previously with chemotherapy, immune checkpoint inhibitors, and antibody-drug conjugates.

The trial was funded by Janssen Research and Development. Dr. Loriot reports grants and personal fees from Janssen, during the conduct of the study.

SOURCE: Loriot Y et al. N Engl J Med. 2019;381:338-348. doi: 10.1056/NEJMoa1817323.

Erdafitinib, an oral pan–fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, is efficacious when used to treat urothelial cancer harboring FGFR genetic alterations, although dose adjustments are commonly needed, suggests a multicenter phase 2 trial.

“Mutations and fusions in FGFR2/3 are common in patients with urothelial carcinoma, particularly in the luminal I subtype, and can cause constitutive FGFR signaling that may contribute to carcinogenesis,” write Yohann Loriot, MD, of Gustave Roussy, Université Paris-Sud and Université Paris-Saclay, in Villejuif, France, and coinvestigators. Up to 20% of patients with advanced disease and fully 37% of those with upper-tract tumors have alterations in these genes. “ Thus, FGFR inhibition may be particularly appropriate in patients with luminal I subtype disease, in which immunotherapeutic approaches may be less effective,” they noted.

In the trial, 99 patients with pretreated locally advanced and unresectable or metastatic urothelial carcinoma having FGFR alterations were given single-agent, open-label erdafitinib (Balversa) for a median of five cycles. The drug was recently granted accelerated approval by the Food and Drug Administration for this indication.

The rate of confirmed response according to investigator assessment was 40% (3% of patients had a complete response and 37% had a partial response), based on trial results reported in the New England Journal of Medicine. The response rate was 59% among the subset who had previously received immunotherapy.

With a median follow-up of 11.0 months, the median duration of progression-free survival was 5.5 months, and the median duration of overall survival was 13.8 months.

Fully 46% of patients experienced a grade 3 or higher treatment-related adverse event, most commonly hyponatremia (11%), stomatitis (10%), and asthenia (7%). Nearly 56% of the trial population as a whole required a dose reduction. However, only 13% of patients stopped treatment because of an adverse event, and there were no treatment-related deaths.

“This study met its primary objective,” Dr. Loriot and coinvestigators concluded. “These findings showed that among patients with locally advanced and unresectable or metastatic urothelial carcinoma with certain FGFR alterations, erdafitinib had promising antitumor activity.”

“The response to erdafitinib was rapid and independent of the number of previous courses and types of therapy, the presence of visceral metastasis, or tumor location,” they wrote. In addition, the efficacy appears to be better than that achieved previously with chemotherapy, immune checkpoint inhibitors, and antibody-drug conjugates.

The trial was funded by Janssen Research and Development. Dr. Loriot reports grants and personal fees from Janssen, during the conduct of the study.

SOURCE: Loriot Y et al. N Engl J Med. 2019;381:338-348. doi: 10.1056/NEJMoa1817323.

Erdafitinib, an oral pan–fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor, is efficacious when used to treat urothelial cancer harboring FGFR genetic alterations, although dose adjustments are commonly needed, suggests a multicenter phase 2 trial.

“Mutations and fusions in FGFR2/3 are common in patients with urothelial carcinoma, particularly in the luminal I subtype, and can cause constitutive FGFR signaling that may contribute to carcinogenesis,” write Yohann Loriot, MD, of Gustave Roussy, Université Paris-Sud and Université Paris-Saclay, in Villejuif, France, and coinvestigators. Up to 20% of patients with advanced disease and fully 37% of those with upper-tract tumors have alterations in these genes. “ Thus, FGFR inhibition may be particularly appropriate in patients with luminal I subtype disease, in which immunotherapeutic approaches may be less effective,” they noted.

In the trial, 99 patients with pretreated locally advanced and unresectable or metastatic urothelial carcinoma having FGFR alterations were given single-agent, open-label erdafitinib (Balversa) for a median of five cycles. The drug was recently granted accelerated approval by the Food and Drug Administration for this indication.

The rate of confirmed response according to investigator assessment was 40% (3% of patients had a complete response and 37% had a partial response), based on trial results reported in the New England Journal of Medicine. The response rate was 59% among the subset who had previously received immunotherapy.

With a median follow-up of 11.0 months, the median duration of progression-free survival was 5.5 months, and the median duration of overall survival was 13.8 months.

Fully 46% of patients experienced a grade 3 or higher treatment-related adverse event, most commonly hyponatremia (11%), stomatitis (10%), and asthenia (7%). Nearly 56% of the trial population as a whole required a dose reduction. However, only 13% of patients stopped treatment because of an adverse event, and there were no treatment-related deaths.

“This study met its primary objective,” Dr. Loriot and coinvestigators concluded. “These findings showed that among patients with locally advanced and unresectable or metastatic urothelial carcinoma with certain FGFR alterations, erdafitinib had promising antitumor activity.”

“The response to erdafitinib was rapid and independent of the number of previous courses and types of therapy, the presence of visceral metastasis, or tumor location,” they wrote. In addition, the efficacy appears to be better than that achieved previously with chemotherapy, immune checkpoint inhibitors, and antibody-drug conjugates.

The trial was funded by Janssen Research and Development. Dr. Loriot reports grants and personal fees from Janssen, during the conduct of the study.

SOURCE: Loriot Y et al. N Engl J Med. 2019;381:338-348. doi: 10.1056/NEJMoa1817323.