PROs From Cisplatin-Ineligible Patients With Advanced or Metastatic UC on EV Alone or With Pembrolizumab

The EV-103 Cohort K trial analyzed the effectiveness of first-line (1L) enfortumab vedotin (EV) with pembrolizumab (P) or EV alone in cisplatin-ineligible patients with locally advanced or metastatic urothelial carcinoma (la/mUC). Researchers presented the results at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium.

The trial showed that EV+P had a significantly meaningful objective response rate (64.5%; 95% CI, 52.7-75.1) and a manageable safety profile. Since Mamtani et al recently reported that la/mUC is associated with symptoms that frequently impact quality of life (QOL) and functioning (J Clin Oncol. 2022;40[16]:4516. doi: 10.1200/JCO.2022.40.16_suppl.4516), researchers analyzed the impact of EV+P or EV alone on QOL and symptoms.

In the open-label phase 1b/2 trial, cisplatin-ineligible patients with la/mUC were randomized 1:1 to receive either EV+P or EV alone. To determine patient-reported outcomes (PRO), patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the Brief Pain Inventory-Short Form (BPI-SF) at baseline, weekly for cycles 1 through 3, and once every cycle for the remainder of the treatment period.

The PRO analysis set included only patients who were treated and had completed the questionnaire at baseline. To determine clinically meaningful change, mixed effect models for repeated measures (MMRM; least squares mean, standard error), not adjusted for multiplicity, estimated change versus baseline until week 24. Established thresholds (EORTC QLQ-C30: 10-point change; BPI-SF: 2-point change) were applied.

Of the 76 patients treated with EV+P, 65 (85.53%) were included in the PRO analysis set. EORTC QLQ-C30 and BPI-SF were completed by 100% and 95% of patients, respectively, at baseline. Compliance rates were ≥84% for both instruments through week 24. In the EORTC QLQ-C30 MMRM analyses, QOL was maintained through week 24 for EV+P; functioning and symptom scores remained stable over time, with improvements in emotional functioning, pain, and sleep disturbance compared with the scores observed at baseline.

In the EV+P arm, clinically meaningful reductions in pain were seen at week 12 (-12.64 [3.208]) compared with baseline and continued through week 24 (-13.20 [3.406]). In the BPI-SF MMRM analyses, worst and average pain, pain interference, and severity consistently showed improved scores from weeks 4 through 24 for EV+P; clinically meaningful change in worst pain was seen at week 21 (-2.08 [0.361]).

Similar completion and compliance rates were seen for the EV alone PRO analysis set (n=63). EV alone demonstrated clinically meaningful improvements in pain at week 24 in the EORTC QLQ-C30 analyses (-10.63 [4.110]), and consistent small-to-moderate improvements in worst and average pain and pain severity (0.5-1.0 points) were seen in the BPI-SF analyses. Improvements in sleep disturbances were noted, and other symptom scales, QOL, and functional domains remained stable.

Overall, PRO data showed that EV+P in cisplatin-ineligible patients with la/mUC was associated with preservation or improvement of QOL, functioning, and symptoms. Improvement in pain was demonstrated consistently in both PRO instruments and both treatment arms.