Erdafitinib (erda) versus available therapies in advanced urothelial cancer: A matching adjusted indirect comparison

Abstract Background Erda, a pan-fibroblast growth factor receptor (FGFR) inhibitor recently received accelerated US FDA approval for locally advanced or metastatic urothelial cancer (mUC) in adult patients (pts) with FGFR2/3 alterations who progressed on ≥ 1 prior platinum-containing chemotherapy, based on a single-arm phase 2 study. In the absence of head-to-head studies, a matching-adjusted indirect comparison (MAIC) was used to compare the efficacy of erda relative to available therapies in mUC pts. Methods Systematic literature review was performed to identify published randomized controlled trials (RCTs) of 2nd-line treatments (from 1990-on) in mUC pts with unknown FGFR status. Individual patient-level data (IPD) were used from the phase 2 study (NCT02365597) in mUC pts treated with erda (8 mg/day). ORR (primary endpoint), overall survival (OS) and progression-free survival (PFS) were compared using an unanchored MAIC. The IPD were weighted to match the aggregated data from comparator studies. Results Nine relevant RCTs of 6 comparators (docetaxel [D], vinflunine [V], pembrolizumab [Pb], atezolizumab [A], paclitaxel [P], and mixed-chemotherapy [D, V or P]) that were identified could be matched with. The matching-adjusted odds ratios (OR) for ORR were consistently >1 vs all comparators, suggesting higher ORR with erda treatment over all comparator 2nd-line therapies. The matching-adjusted hazard ratios (HRs) for OS and PFS vs all comparators were Table . 926P MAIC results for base case scenario: Erda (in FGFR+ pts) vs available 2nd-line therapies in pts with unknown FGFR status Comparator Study N (Neff) ORR (OR [95% CI]) OS (HR [95% CI]) PFS (HR [95% CI]) Pembrolizumab NCT02256436 79 (40) 2.26 [1.11; 4.59] * 0.61 [0.37; 0.99] * 0.77 [0.58; 1.03] Atezolizumab NCT02302807 74 (45) 6.80 [3.55; 13.02] *** 0.58 [0.37; 0.92] * Mixed-chemotherapy NCT02256436 79 (45) 4.15 [2.04; 8.46] *** 0.54 [0.35; 0.85] ** 0.77 [0.56; 1.07] Mixed-chemotherapy NCT02302807 74 (51) 6.26 [3.37; 11.63] *** 0.54 [0.34; 0.84] ** Docetaxela NCT01282463 68 (45) 3.71 [1.11; 12.35] * 0.72 [0.41; 1.25] 0.51 [0.32; 0.80] * Docetaxel NCT00880334 78 (42) 3.98 [1.48; 10.74] ** 0.52 [0.31; 0.87] * 0.84 [0.56; 1.26] Docetaxel NCT01780545 84 (47) 6.02 [2.48; 14.63] *** 0.37 [0.23; 0.61] *** Docetaxel NCT02426125 78 (63) 3.46 [1.80; 6.66] ** 0.63 [0.47; 0.84] * Vinfluninea NCT00315237 78 (53) 4.74 [2.21; 10.18] *** 0.57 [0.39; 0.84] ** Vinflunine NCT01830231 61 (32) 1.51 [0.45; 5.10] 0.49 [0.24; 0.99] * 0.96 [0.51; 1.81] Paclitaxela NCT00949455 68 (44) 2.63 [1.03; 6.73] * 0.59 [0.37; 0.95] * 0.95 [0.64; 1.41] For most comparators, only the main characteristics (according to clinical experts; number of risk factors, ECOG, liver metastases, hemoglobin * p ≤ 0.05; ** p ≤ 0.01; *** p ≤ 0.0001 Conclusions Treatment of FGFR+ mUC pts with erda may be associated with improved overall response, PFS and OS as compared to available therapies in pts with unknown FGFR status. Clinical trial identification NCT02365597. Editorial acknowledgement Priya Ganpathy, MPharm, ISMPP CMPP™ (SIRO Clinpharm Pvt. Ltd, India) provided writing assistance and Harry Ma, PhD (Janssen Global Services) provided additional editorial support. Legal entity responsible for the study Janssen Research & Development, LLC. Funding Janssen Research & Development, LLC. Disclosure Y. Loriot: Honoraria (self), Consultancy / Advisory Role- Astellas Pharma, AstraZeneca, Janssen, Merck Sharp & Dohme, Pfizer, Roche, Ipsen, Seattle Genetics, Sanofi; Research Funding- Sanofi (Inst) S. Van Sanden: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. J. Diels: Shareholder / Stockholder / Stock options, Employee and Share holder: Janssen Reserach & Development. N. Rahhali: Shareholder / Stockholder / Stock options, Employee and stockholder: Janssen Research & Development. D. Seshagiri: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Reserach & Development. B. Kowalski: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Research & Development. S. Fleming: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Research & Development. P. De Porre: Shareholder / Stockholder / Stock options, Employee & stockholder: Janssen Research & Development. A.O. Siefker-Radtke: Consulting / Advisory Role: AstraZeneca, Bristol-Myers Squibb, Eisai, EMD Serono, Genentech, Inovio Pharmaceuticals, Janssen, Lilly, Merck, NCCN; Speakers’ Bureau: Genentech; Research funding: Bristol-Myers Squibb, Janssen, Michael, Sherry Sutton; Fund for Urothelial Cancer: NIH, Takeda; Patents / Royalties / Other Intellectual Property: Methods of characterizing and treating molecular subsets of muscle-invasive bladder cancer.