ERDAFITINIB in locally advanced or metastatic urothelial carcinoma (mUC): Long-term outcomes in BLC2001.

Abstract

5015 Background: Erdafitinib (JNJ-42756493; ERDA) is the only pan-FGFR kinase inhibitor with US FDA approval for treatment of adults with mUC with susceptible FGFR3/2 alterations (alt) and who progressed on ≥ 1 line of prior platinum-based chemotherapy (chemo). Approval was based on data from the primary analysis of the pivotal BLC2001 trial1. Here we report long-term efficacy and safety data from the 8 mg/d continuous dose regimen in BLC2001. Methods: BLC2001 (NCT02365597) is a global, open-label, phase 2 trial of pts with measurable mUC with prespecified FGFR alt, ECOG 0-2, and progression during/following ≥ 1 line of prior chemo or ≤ 12 mos of (neo)adjuvant chemo, or were cisplatin ineligible, chemo naïve. The optimal schedule of ERDA determined in the initial part of the study was 8 mg/d continuous ERDA in 28-d cycles with uptitration to 9 mg/d (ERD 8 mg UpT) if a protocol-defined target serum phosphate level was not reached and if no significant treatment-related adverse events (TRAEs) occurred. Primary end point was the confirmed objective response rate (ORR=% complete response + % partial response). Key secondary end points were progression-free survival (PFS), duration of response (DOR) and overall survival (OS). Results: Median follow-up for 101 patients treated with ERDA 8 mg UpT was ~24 months. Confirmed ORR was 40%. Median DOR was 5.98 mos; 31% of responders had DOR ≥ 1 yr. Median PFS was 5.52 mos, median OS was 11.3 mos. 12-mos and 24-mos survival rates were 49% and 31%, respectively. Median treatment duration was 5.4 mos. The ERDA safety profile was consistent with the primary analysis. No new TRAEs were seen with longer follow-up. Central serous retinopathy (CSR) events occurred in 27% (27/101) of patients; 85% (23/27) were Grade 1 or 2; dosage was reduced in 13 pts, interrupted for 8, and discontinued for 3. On the data cut-off date, 63% (17/27) had resolved; 60% (6/10) of ongoing CSR events were Grade 1. There were no treatment-related deaths. Conclusions: With a median follow-up of 2 yrs, ERDA in mUC + FGFR alt showed a manageable safety profile and consistent efficacy, with median OS of 11.3 mos. 31% had a DOR ≥12 mos and 31% were alive at 24 mos. ERDA monotherapy vs. immune checkpoint inhibitor (PD-1) or chemo is being further analyzed in a randomized control study (THOR; NCT03390504).Reference: Loriot Y, et al. N Engl J Med. 2019;381:338-48. Clinical trial information: NCT02365597 .

New and Emerging Therapies in the Management of Bladder Cancer

“…A total of 22 patients had previously received immunotherapy with only one achieving a response, yet the response rate for erdafitinib for this subgroup was 59%. At a median follow-up of 24 months, the median PFS was 5.5 months (95% CI 4.0–6.0) and the median OS was 11.3 months (95% CI 9.7–15.2) 34 . Based on these results, erdafitinib was approved by the FDA in April 2019 for patients with mUC with a susceptible FGFR2/3 alteration following platinum-containing chemotherapy.…”

Novel Tyrosine Kinase Targets in Urothelial Carcinoma

“…mPFS was 5.52 months and mOS was 11.3 months. Central serous retinopathy (CSR) occurred in 27% (27/101) of patients, but 85% of those (23/27) were grade 1 or 2 [ 62 ]. In addition, a phase III trial is evaluating erdafitinib compared to pembrolizumab or CT in patients with mUC and FGFR alterations who have progressed after one or two prior treatments (NCT03390504) [ 63 ].…”

Fibroblast Growth Factor Receptor (FGFR) Inhibitors in Urothelial Cancer

“…Of the 22 patients who received prior immunotherapy, the response rate was 59% with erdafitinib. After a follow up of 2 years, the median PFS was 5.5 months (95% CI, 4.2–6.0), and the median OS was 11.3 months [23]. The most common treatment‐related adverse events (AEs) included hyperphosphatemia (77%), stomatitis (58%), diarrhea (50%), and dry mouth (46%) [22].…”