Erdafitinib Achieves Responses Across Multiple Cancer Types With FGFR Alterations

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Three clinical trials demonstrated positive results from the targeted therapy erdafitinib for patients with multiple tumor types harboring FGFR alterations. The data were presented at the 2023 ASCO Annual Meeting. Erdafitinib is an oral medication that blocks the activity of FGFR signaling proteins, which are important for a variety of normal cellular processes. However, FGFR genetic alterations can drive the development of many cancer types, including urothelial, bile duct, breast, stomach, liver, and lung cancers. Erdafitinib was the first approved FGFR-targeted therapy and is the only approved FGFR-targeted option for advanced urothelial cancer.

Erdafitinib Demonstrates Tumor-Agnostic Benefits Across 16 Cancer Types

The tumor-agnostic Phase II RAGNAR trial, led by Shubham Pant, MD, Professor of Gastrointestinal Medical Oncology and Investigational Cancer Therapeutics at The University of Texas MD Anderson Cancer Center, confirmed the efficacy of erdafitinib in heavily pretreated patients with advanced FGFR-altered solid tumors across 16 distinct cancer types (Abstract 3121).

Shubham Pant, MD

Shubham Pant, MD

Among 217 patients on the trial, the overall response rate was 29.5%, including 6 complete responses and 58 partial responses. The overall response rate was comparable across FGFR1-3 mutations and fusions. The treatment achieved a disease control rate of 73.7% and a clinical benefit rate of 45.6%, including an overall response rate of 56% in patients with pancreatic cancer and 52% in patiets with cholangiocarcinoma.

“This study represents the largest tumor-agnostic trial of a targeted therapy to date, and the results demonstrate that erdafitinib provides meaningful clinical benefit in patients with advanced FGFR-altered solid tumors,” Dr. Pant said. “These findings suggest erdafitinib may be an important option, regardless of tumor type, for patients with FGFR alternations who have exhausted other available therapies.”

The ongoing open-label, single-arm RAGNAR trial enrolled adult and pediatric patients with FGFR­-altered advanced solid tumors, excluding urothelial cancers. All patients had disease progression after at least one prior systemic therapy and had no alternative treatment options.

The median age of participants was 57 years (range = 12–79 years), and patients had received a median of two prior lines of therapy. The study included patients with central nervous system tumors, gastrointestinal cancers, gynecologic cancers, lung cancers, and other rare tumors.

All but one patient experienced treatment-emergent side effects, and 70% of participants experienced grade 3 or higher adverse events. The safety profile was consistent with the known side effects seen in previous trials.

Adding Immunotherapy to Erdafitinib Elevates Response Rates in Advanced Urothelial Cancer

The phase II NORSE study, led by Arlene Siefker-Radtke, MD, Professor of Genitourinary Medical Oncology at MD Anderson, demonstrated clinically meaningful improvements when adding the immunotherapy cetrelimab to erdafitinib for patients with FGFR-altered metastatic urothelial cancer (Abstract 4504).

The combination of erdafitinib with cetrelimab, an anti–PD-1 immune checkpoint inhibitor, achieved an overall response rate of 54.5% across 44 patients, with six complete responses, and an overall survival rate of 68% at 12 months. In comparison, erdafitinib alone achieved an overall response rate of 44.2% in 43 patients, including one complete response, and a 12-month overall survival rate of 56%.

Arlene Siefker-Radtke, MD

Arlene Siefker-Radtke, MD

FGFR-altered tumors typically are immunologically cold and have limited responses to immunotherapy. The goal of this trial was to determine if combining immunotherapy and FGFR-targeted therapy could improve response rates,” Dr. Siefker-Radtke said. “We are encouraged by the promising responses and median survival results, and we look forward to future studies to learn the full impact for our patients.”

Standard therapy for patients with advanced urothelial cancer is cisplatin-based chemotherapy, but this regimen has significant side effects and cannot be tolerated by all patients. This open-label study was designed to evaluate the safety and efficacy of erdafitinib plus cetrelimab vs erdafitinib alone in adult patients who had received prior systemic therapy and were ineligible for cisplatin-based therapies.

As of the data cutoff, the trial randomly assigned 87 patients across the treatment arms. Median patient ages were 69 years and 72 years in the combination and monotherapy arms, respectively. The median follow-up time was 14.2 months.

The combination presented a safety profile consistent with that of erdafitinib and cetrelimab alone. Grade 3 treatment-related adverse events occurred in 45.5% of patients receiving the combination treatment and 46.5% of patients receiving erdafitinib alone. There was one cetrelimab-related patient death in the combination arm that occurred secondary to pulmonary failure.

Erdafitinib Improves Patient Outcomes over Chemotherapy in FGFR-Altered Urothelial Cancer

According to results from cohort one of the phase III THOR trial, erdafitinib significantly improved survival and response outcomes relative to standard chemotherapy for patients with advanced or metastatic urothelial cancer with FGFR alterations (Abstract LBA4619).

With 266 patients randomly assigned to receive either erdafitinib or chemotherapy, the median overall survival was 12.1 and 7.8 months, respectively, corresponding to a 36% lower risk of death for those treated with erdafitinib. Further, patients treated with erdafitinib achieved a median progression-free survival of 5.6 months compared to just 2.7 months for those receiving standard chemotherapy. Nearly half (46%) of patients treated with erdafitinib saw their tumors shrink, while just 12% on the chemotherapy arm had an objective response.

“These results demonstrate improved responses and survival outcomes for patients receiving erdafitinib compared to standard-of-care chemotherapy, confirming the benefit for these patients,” said Dr. Siefker-Radtke, who was a senior investigator on the trial. “This highlights the significance of a targeted therapy option for patients with FGFR-altered urothelial cancer and is the first biomarker-targeted therapy for this disease.”

Erdafitinib was approved in 2019 by the U.S. Food and Drug Administration for advanced FGFR-altered urothelial cancer based on the results of a phase II trial led by Dr. Siefker-Radtke. The THOR trial reinforces the benefits over standard therapeutic options for these patients.

The trial enrolled adults with advanced/metastatic urothelial cancer harboring specific FGFR alterations. All patients had experienced disease progression after two or fewer prior lines of therapy, including chemotherapy and immunotherapy. Patients were randomly assigned to receive erdafitinib (n = 136) or the investigator’s choice of chemotherapy (n = 130). The patients' median age was 67 years.

Cohort one of the trial met its primary endpoint of improved overall survival and was concluded based on achieving predefined superiority criteria. The side effects of the treatment were consistent with the known safety profile of erdafitinib.

Disclosure: For full disclosures of the study authors, visit (Abstract 3121, Abstract 4504, Abstract LBA4619).

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.