Health-related quality of life (HRQOL) with pembrolizumab or observation for high-risk muscle-invasive urothelial carcinoma after surgery: Results from the AMBASSADOR randomized trial (Alliance A031501).

4513 Background: The AMBASSADOR trial (NCT03244381) showed that in patients with high-risk muscle-invasive urothelial carcinoma after radical surgery, adjuvant pembrolizumab for one year improved disease-free survival from 14.2 to 29.6 months (Apolo et al, NEJM 2024). Here we report the HRQOL results. Methods: HRQOL was completed by 560 randomized patients and included the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 plus the bladder cancer supplement BLM30, and the EQ-5D-5L, which assesses overall quality of life or health state. Published minimally important difference thresholds for EQ-5D-5L is 0.06, and for EORTC instruments is 5-10 points. For all reported HRQOL data, higher score is better except BLM30 urinary symptoms, where higher score indicates more symptoms. Results: Mean changes from baseline to 12 months (corresponding to end of treatment) for each HRQOL measure are summarized in the Table. No statistically significant difference was seen between the observation vs. pembrolizumab arms. Further, numerical differences between arms for these HRQOL measures do not meet (are lower than) the published minimally clinically important difference thresholds. Conclusions: Adjuvant pembrolizumab after radical surgery for patients with high-risk muscle-invasive urothelial carcinoma improved disease-free survival without negatively affecting HRQOL. These HRQOL results add further support to adjuvant immune checkpoint blockade therapy in these patients. Support: U10CA180821, U10CA180882, UG1CA189823 (https://acknowledgments.alliancefound.org). Clinical trial information: NCT03244381 . HRQOL mean change from baseline to 12 months and between-arm comparisons. A) Observation B) Pembrolizumab Difference A vs B P-value EQ-5D-5L Index Value -.029 -.012 -.02 .45 QLQ-C30 Global Health 0.07 1.45 -1.38 .55 QLQ-C30 Physical Functioning -.089 -.069 -0.02 .99 QLQ-C30 Role Functioning 3.22 -1.23 4.45 .15 BLM30 Urinary Symptoms -3.44 -3.02 -.42 .87 BLM30 Sexual Functioning -.53 4.15 -4.68 .07