4510 Background: In KEYNOTE-905/EV-303 (NCT03924895), neoadj-adj EV + pembro and radical cystectomy (RC) + pelvic lymph node dissection (PLND) showed significant and meaningful improvements in EFS, OS, and pathologic complete response vs RC + PLND in pts with MIBC who were ineligible for or declined cisplatin (cis) therapy. Prespecified exploratory HRQoL outcomes are reported. Methods: Pts with MIBC who were ineligible/declined cis were randomized 1:1 to neoadj-adj EV + pembro and RC + PLND or RC + PLND (control). HRQoL was analyzed in pts who completed ≥1 PRO assessment. EQ-5D-5L and Functional Assessment of Cancer Therapy (FACT)–Bladder-Cystectomy (Bl-Cys) with FACT-general (FACT-G) and Bladder Cancer Index (BCI) were assessed predose on D1 of neoadjuvant cycles 1 (baseline BL), 2, and 3; pre- and post-surgery; and predose on D1 of adjuvant cycles 1, 2, 4, 8, and 12 in the EV + pembro arm. In the control arm, assessments were at pre- (BL) and post-surgery. In both treatment (Tx) arms, assessments were also done at Tx discontinuation, Q12W for ≤2y, and Q24W thereafter. End points included mean (95% CI) change from BL to post-surgery wk 18 in FACT-G score; FACT–Bl-Cys scores (Bl-Cys subscale and Trial Outcome Index TOI); BCI urinary, bowel, and sexual scores; and EQ-5D-5L visual analog scale (VAS). Results: At post-surgery wk 18, completion and compliance rates for all assessments were ≥65% in the EV + pembro arm and >86% in the control arm. Mean changes from BL to post-surgery wk 18 were similar between arms for FACT-G total and FACT–Bl-Cys subscale scores; FACT–Bl-Cys TOI score; BCI urinary, bowel, and sexual scores; and EQ-5D-5L VAS score (Table). BCI sexual and bowel score diminution was observed in both arms. For all PRO assessments, mean changes from BL over time were similar between Tx. Conclusions: The addition of neoadj-adj EV + pembro did not decrease HRQoL 18 wk post-surgery relative to RC + PLND alone; BCI bowel and sexual domains worsened in both arms, consistent with prior reports of RC impact. Given the superior efficacy and manageable safety, these results support the benefit/risk profile of EV + pembro and RC + PLND as Tx for pts with MIBC ineligible for or declining cis. Clinical trial information: NCT03924895 . Mean change from BL to post-surgery wk 18, (95% CI), n EV + pembro Control FACT-G total score −2.73 (−6.22 to 0.75)n = 102 −2.84 (−6.11 to 0.43)n = 75 FACT–Bl-Cys (subscale/symptom index) total score 1.31 (−0.70 to 3.32)n = 102 1.85 (−0.59 to 4.29)n = 75 FACT–Bl-Cys TOI −1.89 (−5.61 to 1.84)n = 102 −0.58 (−4.35 to 3.20)n = 75 BCI urinary −2.03 (−6.12 to 2.07)n = 101 −0.05 (−5.90 to 5.80)n = 70 BCI bowel −4.75 (−8.73 to −0.77)n = 101 −4.27 (−7.93 to −0.61)n = 70 BCI sexual −15.46 (−20.53 to −10.39)n = 94 −17.88 (−24.36 to −11.40)n = 61 EQ-5D-5L VAS −2.52 (−7.23 to −2.19)n = 102 −0.39 (−5.14 to 4.36)n = 75
O'Donnell et al. (Wed,) studied this question.