745P Patient-reported outcomes (PROs) from JAVELIN Bladder 100: Avelumab first-line (1L) maintenance + best supportive care (BSC) vs BSC alone for advanced urothelial carcinoma (UC)

Abstract

association of these sigs with efficacy in the phase 3 KEYNOTE-045 trial of pembro vs chemo in platinum-refractory metastatic UC (mUC).Methods: Univariate analyses using logistic regression (ORR) and Cox proportional hazard (PFS, OS), adjusted for ECOG PS, were performed, and nominal P values (1sided, pembro; 2-sided, chemo) without multiplicity adjustment were calculated. Significance was prespecified at 0.05. Clinical utility of GEP and stromal sig was assessed using first tertile and median cutoffs.Results: 291/542 pts (53.7%) had RNA-seq data. GEP was associated with ORR (P¼0.05) with pembro; a positive trend was observed for PFS (P¼0.09) and OS (P¼0.12). GEP was not associated with ORR (P¼0.87), PFS (P¼0.58), or OS (P¼0.98) with chemo. HR estimates using prespecified GEP cutoff suggest trends toward improved PFS and OS for pembro vs chemo in GEP-high group (Table ). Stromal sig was not associated with outcomes with pembro (P¼0.15 [ORR], 0.30 [PFS], 0.40 [OS]) or chemo (P¼0.42 [ORR], 0.09 [PFS], 0.12 [OS]). HR estimates using prespecified stromal sig cutoff suggest trends toward longer PFS and OS in median group; this may be driven by poor performance of chemo in this group vs the hypothesized association with pembro (Table ). Conclusions:In this exploratory analysis in pts with mUC from KEYNOTE-045, GEP was positively associated with ORR to pembro but not chemo. GEP continues to serve as a good exploratory gene sig to support the MOA of pembro in highly inflamed tumors. Stromal sig was not associated with outcomes to pembro in KEYNOTE-045. Additional analyses are exploring differences in association of stromal sig with pembro between KEYNOTE-052 and KEYNOTE-045.Clinical trial identification: NCT02256436.

Avelumab first-line maintenance in locally advanced or metastatic urothelial carcinoma: Applying clinical trial findings to clinical practice

“…Furthermore, median time to deterioration in the NCCN Functional Assessment of Cancer Therapy Bladder Cancer Symptom Index-18 (NFBISI-18) disease-related symptoms-physical subscale was similar between arms. Thus, avelumab 1L maintenance prolonged OS with no detrimental effect on clinically relevant PROs [97].…”

The Rapidly Evolving Landscape of First-Line Targeted Therapy in Metastatic Urothelial Cancer: A Systematic Review

“…Median PFS was longer for avelumab (3.7 vs. 2.0 months; HR, 0.62; 95% CI, 0.52-0.75; p = not reported). Mean changes from baseline for the Functional Assessment of Cancer Therapy -Bladder Symptom Index (FBISI-18) and EuroQol-5 Dimension-5 Level (EQ-5D-5L) QoL scores were similar between treatment arms [45]. ORRs were higher for avelumab compared with the control arm, although DoRs were not reported [43].…”

Avelumab First-Line Maintenance Treatment in Advanced Bladder Cancer: Practical Implementation Steps for Infusion Nurses

“…27 The study also showed that avelumab maintenance treatment did not negatively affect clinically relevant patient-reported outcomes, where the median time to deterioration was not reached for avelumab plus BSC (95% CI, 13.9 months to not estimable) versus BSC alone (95% CI, 12.9 months to not estimable) at 13.8 months. 42 Treatmentrelated adverse events (AEs), of which the most common (≥10% of patients) included pruritus, hypothyroidism, diarrhea, and infusion-related reaction, occurred more frequently in the avelumab arm (active treatment) than in the BSC arm (no active treatment; Figure 4). 27 Discontinuation rates due to AEs were low with avelumab, and the toxicity profile seems to be consistent with that reported in other trials of ICIs, with the most common (67% of patients) AEs of any cause being fatigue, nausea, diarrhea, and increased serum biomarkers.…”