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

Abstract

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 2 nd -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 (8mg/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 2 nd -line therapies. The matching-adjusted hazard ratios (HRs) for OS and PFS vs all comparators were <1, suggesting better outcomes (PFS/OS) with erda. Results from the sensitivity analyses showed varied statistical significance, however, the overall trends were relatively similar. Study limitations: availability of comparable endpoints and baseline characteristics; small sample size of the erda study.Table926P MAIC results for base case scenario: Erda (in FGFR+ pts) vs available 2 nd -line therapies in pts with unknown FGFR statusTableComparatorStudyN (N eff)ORR (OR [95% CI])OS (HR [95% CI])PFS (HR [95% CI])PembrolizumabNCT0225643679 (40)2.26 [1.11; 4.59]*0.61 [0.37; 0.99]*0.77 [0.58; 1.03]AtezolizumabNCT0230280774 (45)6.80 [3.55; 13.02]***0.58 [0.37; 0.92]*Mixed-chemotherapyNCT0225643679 (45)4.15 [2.04; 8.46]***0.54 [0.35; 0.85]**0.77 [0.56; 1.07]Mixed-chemotherapyNCT0230280774 (51)6.26 [3.37; 11.63]***0.54 [0.34; 0.84]**Docetaxel a NCT0128246368 (45)3.71 [1.11; 12.35]*0.72 [0.41; 1.25]0.51 [0.32; 0.80]*Docetaxe…