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Clinical Trial
. 2024 Apr 20;42(12):1403-1414.
doi: 10.1200/JCO.23.01547. Epub 2024 Jan 12.

Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab

Matthew I Milowsky  1 , Peter H O'Donnell  2 , Christopher J Hoimes  3 , Daniel P Petrylak  4 , Thomas W Flaig  5 , Helen H Moon  6 , Terence W Friedlander  7 , Nataliya Mar  8 , Rana R McKay  9 , Sandy Srinivas  10 , Gwenaelle Gravis  11 , Chethan Ramamurthy  12 , Manojkumar Bupathi  13 , Sergio Bracarda  14 , Phoebe Wright  15 , Zsolt Hepp  15 , Anne-Sophie Carret  15 , Yao Yu  15 , Ryan Dillon  16 , Ritesh Kataria  17 , Jennifer L Beaumont  18 , Intan Purnajo  18 , Jonathan E Rosenberg  19
Affiliations
Clinical Trial

Patient-Reported Outcomes in Patients With Advanced Urothelial Cancer Who Are Ineligible for Cisplatin and Treated With First-Line Enfortumab Vedotin Alone or With Pembrolizumab

Matthew I Milowsky et al. J Clin Oncol. .

Abstract

Purpose: Locally advanced/metastatic urothelial cancer (la/mUC) affects patients' quality of life (QOL) and functioning. We describe the impact of first-line (1L) enfortumab vedotin (EV) alone or with pembrolizumab (P) on QOL/functioning/symptoms in patients with la/mUC who were cisplatin-ineligible from EV-103 Cohort K.

Methods: In this phase Ib/II trial, patients were randomly assigned 1:1 to EV + P or EV monotherapy (mono). Exploratory patient-reported outcomes (PROs) were assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30) and Brief Pain Inventory Short Form (BPI-SF) at baseline, once per week for cycles 1-3, and then in every cycle through the end of treatment. Changes in scores from baseline to week 24, reported as least squares mean (standard error), were assessed by mixed models for repeated measures. There were no formal statistical comparisons between treatment arms.

Results: Of 149 patients treated, 65 (EV + P) and 63 (EV mono) comprised the PRO analysis set. For EV + P, EORTC QLQ-C30 QOL was maintained through week 24 with improvements in emotional functioning, pain, and insomnia. Clinically meaningful improvements were seen in EORTC QLQ-C30 pain after EV + P at weeks 12 (-14.41 [3.14]) and 24 (-14.99 [3.56]) and BPI-SF worst pain at week 24 (-2.07 [0.37]). For EV mono, EORTC QLQ-C30 QOL remained stable with clinically meaningful improvements in EORTC QLQ-C30 pain (-12.55 [4.27]), insomnia (-14.46 [4.69]), and constipation (-10.09 [4.35]) at week 24. There were small-to-moderate improvements in BPI-SF worst pain at week 24.

Conclusion: EV + P in patients with la/mUC who were cisplatin-ineligible was associated with preservation or improvement of QOL/functioning/symptoms. Improvement in pain was seen in both PRO instruments and treatment arms. These data complement clinical outcomes of 1L EV + P.

Trial registration: ClinicalTrials.gov NCT03288545.

PubMed Disclaimer

Conflict of interest statement

The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/authors/author-center.

Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments).

Figures

FIG 1.
FIG 1.
(A) EORTC QLQ-C30a QOL and functioning scales and (B) EORTC QLQ-C30 symptom scales in the EV + P arm over a 24-week follow-up period. aFor MMRM analyses, treatment and time (and their interaction), baseline PRO, liver metastases, and ECOG PS were included in the model. Line plots show adjusted LS means of predicted change from baseline for all postbaseline assessments. Clinically meaningful improvements were identified using a predefined threshold (10-point change) for the EORTC QLQ-C30. bFor appetite loss, n = 42 at week 8. ECOG PS, Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core Questionnaire; EV, enfortumab vedotin; GHS, global health status; la/mUC, locally advanced/metastatic urothelial cancer; LS, least square; MMRM, mixed models for repeated measures; P, pembrolizumab; PRO, patient-reported outcome; QOL, quality of life.
FIG 2.
FIG 2.
(A) EORTC QLQ-C30a QOL and functioning scales and (B) EORTC QLQ-C30 symptom scales in the EV mono arm over a 24-week follow-up period. aFor MMRM analyses, treatment and time (and their interaction), baseline PRO, liver metastases, and ECOG PS were included in the model. Line plots show adjusted LS means of predicted change from baseline until week 24. Clinically meaningful improvements were identified using a predefined threshold (10-point change) for the EORTC QLQ-C30. bFor physical functioning and role functioning, n = 45 at week 15. cFor diarrhea, n = 44 at week 15. ECOG PS, Eastern Cooperative Oncology Group performance status; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core Questionnaire; EV, enfortumab vedotin; GHS, global health status; LS, least square; MMRM, mixed models for repeated measures; mono, monotherapy; PRO, patient-reported outcome; QOL, quality of life.
FIG 3.
FIG 3.
(A) BPI-SF worst pain scoresa and (B) pain interference in the EV + P arm over a 24-week follow-up period. aFor MMRM analyses, treatment and time (and their interaction), baseline PRO, liver metastases, and ECOG PS were included in the model. Line plots show adjusted LS means of predicted change from baseline for all postbaseline assessments. Clinically meaningful improvements were identified using a predefined threshold (2-point change) for the BPI-SF. BPI-SF, Brief Pain Inventory Short Form; ECOG PS, Eastern Cooperative Oncology Group performance status; EV, enfortumab vedotin; LS, least square; MMRM, mixed models for repeated measures; P, pembrolizumab; PRO, patient-reported outcome.
FIG 4.
FIG 4.
(A) BPI-SF worst pain scoresa and (B) pain interference in the EV mono arm over a 24-week follow-up period. aFor MMRM analyses, treatment and time (and their interaction), baseline PRO, liver metastases, and ECOG PS were included in the model. Line plots show adjusted LS means of predicted change from baseline for all postbaseline assessments. Clinically meaningful improvements were identified using a predefined threshold (2-point change) for the BPI-SF. BPI-SF, Brief Pain Inventory Short Form; ECOG PS, Eastern Cooperative Oncology Group performance status; EV, enfortumab vedotin; LS, least square; MMRM, mixed models for repeated measures; mono, monotherapy; PRO, patient-reported outcome.
FIG A1.
FIG A1.
PRO instruments and assessment schedule for the PRP. All analyses were conducted in the PRP unless otherwise specified. The PRP included any patients who completed at least one question of the PRO questionnaire at baseline. aA 30-item questionnaire to assess QOL in patients with cancer; scores range from 0 to 100. bAn eight-item questionnaire assessing the severity of pain and its impact on functioning in terms of worst, least, and average pain in the past 24 hours; scores range from 0 to 10. cAfter EOT, patients completed PROs once every 9 weeks until 1 year and then every 12 weeks thereafter through long-term follow-up; those data are not presented here. BPI-SF, Brief Pain Inventory Short Form; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire–Core Questionnaire; EOT, end of treatment; GHS, global health status; PRO, patient-reported outcome; PRP, patient-reported outcome population; QOL, quality of life.
FIG A2.
FIG A2.
Responder analysis for BPI-SF worst pain over the 24-week follow-up period in the EV + P arm. All analyses were conducted in the PRP unless otherwise specified; the PRP included patients who completed at least one question of the PRO questionnaires at baseline. Sample sizes for some analyses are smaller because of missing data. An improvement in pain was defined as a decrease in score from baseline by at least one MCT, pain reported as stable was defined as a change in score from baseline within one MCT, and a worsening in pain was defined as an increase in score from baseline by at least one MCT. The BPI-SF is an eight-item questionnaire assessing the severity of pain and its impact on functioning in terms of worst, least, and average pain in the past 24 hours; scores range from 0 to 10. Higher scores are associated with more pain; a 2-point MCT was applied. BPI-SF, Brief Pain Inventory Short Form; EV, enfortumab vedotin; MCT, meaningful change threshold; P, pembrolizumab; PRO, patient-reported outcome; PRP, patient-reported outcome population.
FIG A3.
FIG A3.
Responder analysis for BPI-SF worst pain over the 24-week follow-up period in the EV mono arm. All analyses were conducted in the PRP unless otherwise specified; the PRP included patients who completed at least one question of the PRO questionnaires at baseline. Sample sizes for some analyses are smaller because of missing data. An improvement in pain was defined as a decrease in score from baseline by at least one MCT, pain reported as stable was defined as a change in score from baseline within one MCT, and a worsening in pain was defined as an increase in score from baseline by at least one MCT. The BPI-SF is an eight-item questionnaire assessing the severity of pain and its impact on functioning in terms of worst, least, and average pain in the past 24 hours; scores range from 0 to 10. Higher scores are associated with more pain; a 2-point MCT was applied. BPI-SF, Brief Pain Inventory Short Form; EV, enfortumab vedotin; MCT, meaningful change threshold; mono, monotherapy; PRO, patient-reported outcome; PRP, patient-reported outcome population.
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