TY - JOUR
T1 - Patient-reported outcomes and inflammatory biomarkers in patients with locally advanced/metastatic urothelial carcinoma treated with durvalumab in phase 1/2 dose-escalation study 1108
AU - O'Donnell, Peter H.
AU - Arkenau, Hendrick Tobias
AU - Sridhar, Srikala S.
AU - Ong, Michael
AU - Drakaki, Alexandra
AU - Spira, Alexander I.
AU - Zhang, Jingsong
AU - Gordon, Michael S.
AU - Degboe, Arnold N.
AU - Gupta, Ashok K.
AU - Mukhopadhyay, Pralay
AU - Huang, Wenmei
AU - Abdullah, Shaad E.
AU - Angra, Natasha
AU - Roskos, Lorin K.
AU - Guo, Xiang
AU - Friedlander, Terence
N1 - Funding Information:
Peter H. O'Donnell has received honoraria from Genentech/Roche, Merck, AstraZeneca, Astellas Pharma, Seattle Genetics, Inovio Pharmaceuticals, Janssen Biotech, Parexel, Kantar Health, Harrison Consulting Group, Quintiles, and OncLive; has acted in a consulting/advisory role for Merck; has received funding from Merck, Boehringer Ingelheim, Genentech/Roche, AstraZeneca, Acerta Pharma, Janssen, Seattle Genetics, and Bristol‐Myers Squib; and has received travel/accommodations or expenses from Merck and Seattle Genetics/Astellas. Srikala S. Sridhar reports consulting/advisory work with AstraZeneca, Roche, Pfizer, Bristol‐Myers Squib, and Merck. Michael Ong has accepted expenses from the study sponsor, AstraZeneca, and reports personal fees from Merck, Bristol‐Myers Squibb, EMD Serono, and Johnson & Johnson and consulting for Janssen. Alexandra Drakaki has participated in projects for Bristol‐Myers Squibb, AstraZeneca, Radmetrix, and Kynan; has accepted research funding and other funding/expenses from Kite/Gilead and Lilly; and reports equity in Kynan Pharma, Medicus Data, Urogen, and Allogene. Alexander I. Spira has received personal fees from Array, Mirati, Novartis, Roche, Bluepoint, Merck, CytomX, and AstraZeneca; grants from AbbVie, Roche, Novartis, Arch, Mirati, Takeda, and CytomX; and nonfinancial support from CytomX. Jingsong Zhang has received research funding and honoraria from AstraZeneca, has participated as a speaker for AstraZeneca, and has acting in a consulting/advisory role for the company. Michael S. Gordon reports institutional research support from Medimmune, Merck, Bristol‐Myers Squib, Amgen, Tesaro, BeiGene, AbbVie, Aeglea, Agenus, Arcus, Astex, BluePrint, Calithera, Celldex, Corcept, Clovis, Eli Lilly, Endocyte, Five Prime, Genocea, Neon, Plexxikon, Imaging Endpoints, Revolution Medicine, Seattle Genetics, Serono, SynDevRx, Toleron, Tracon, Deciphera, and Salarius and personal fees from Agenus, Imaging Endpoints, Tracon, Deciphera, and Salarius. Arnold N. Degboe and Pralay Mukhopadhyay are full‐time employees of the study sponsor, AstraZeneca, and Mukhopadhyay owns stock in AstraZeneca. Ashok K. Gupta is a full‐time employee of the study sponsor, AstraZeneca, and owns stock in AstraZeneca, Bristol‐Myers Squibb, and MacroGenics; in addition, Gupta is a coauthor of a Bristol‐Myers Squibb patent. Wenmei Huang was a full‐time employee of the study sponsor, AstraZeneca, during the study period and also owns stocks in AstraZeneca. Shaad E. Abdullah is a full‐time employee of MedImmune and owns stock in MedImmune and AstraZeneca. Natasha Angra, Lorin K. Roskos, and Xiang Guo are full‐time employees of MedImmune and own stock in Medimmune. Terence Friedlander has participated in Bristol‐Myers Squibb and AstraZeneca projects, including an AstraZeneca advisory board, and reports personal fees from Astra Zeneca, Genentech, Pfizer, and Janssen. The other authors made no disclosures.
Publisher Copyright:
© 2019 American Cancer Society
PY - 2020/1/15
Y1 - 2020/1/15
N2 - Background: Durvalumab has shown meaningful clinical activity in patients with metastatic urothelial carcinoma (mUC) in Study 1108 (NCT01693562). An important focus in treatment is health-related quality of life (HRQOL). Here, patient-reported outcomes (PROs) from Study 1108 and their relationship with inflammatory biomarkers are explored. Methods: Disease-related symptoms, functioning, and HRQOL were assessed with the Functional Assessment of Cancer Therapy–Bladder (FACT-Bl) and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Relationships between PRO improvements and the best changes in the tumor size, albumin level, and neutrophil-lymphocyte ratio (NLR) were assessed with Spearman correlation analysis. Results: The mean FACT-Bl total score improved from 107.5 (standard deviation [SD], 23.0) at the baseline to 115.4 (SD, 22.6) on day 113, with similar increases found for the Trial Outcome Index (TOI) and Bladder Cancer Subscale (BLCS) scores. The mean FACT-Bl total scores improved over time, and the FACT-Bl TOI scores significantly improved by day 113 (P <.05). The mean EORTC QLQ-C30 Global Health Status/Quality of Life score improved from 57.1 (SD, 24.8) at the baseline to 69.0 (SD, 21.4) on day 113; the functional scale and symptom scores (day 113) were higher than the baseline scores (P <.05) for EORTC Social Functioning. The FACT-Bl total, BLCS, and TOI scores improved in 32.6%, 34.9%, and 32.6% of the patients by day 113; 26.3% to 37.8% of the patients exhibited improvements in EORTC QLQ-C30 functional scores. The best tumor shrinkage and posttreatment improvements in serum albumin and NLR correlated with increases in FACT-Bl total, TOI, and BLCS scores and in EORTC Physical Functioning and Role Functioning scores (P <.05). Conclusions: Durvalumab was associated with improvements in disease-related symptoms, functioning, and HRQOL in patients with mUC. Improvements in systemic inflammation may contribute to PRO improvements in these patients.
AB - Background: Durvalumab has shown meaningful clinical activity in patients with metastatic urothelial carcinoma (mUC) in Study 1108 (NCT01693562). An important focus in treatment is health-related quality of life (HRQOL). Here, patient-reported outcomes (PROs) from Study 1108 and their relationship with inflammatory biomarkers are explored. Methods: Disease-related symptoms, functioning, and HRQOL were assessed with the Functional Assessment of Cancer Therapy–Bladder (FACT-Bl) and the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Relationships between PRO improvements and the best changes in the tumor size, albumin level, and neutrophil-lymphocyte ratio (NLR) were assessed with Spearman correlation analysis. Results: The mean FACT-Bl total score improved from 107.5 (standard deviation [SD], 23.0) at the baseline to 115.4 (SD, 22.6) on day 113, with similar increases found for the Trial Outcome Index (TOI) and Bladder Cancer Subscale (BLCS) scores. The mean FACT-Bl total scores improved over time, and the FACT-Bl TOI scores significantly improved by day 113 (P <.05). The mean EORTC QLQ-C30 Global Health Status/Quality of Life score improved from 57.1 (SD, 24.8) at the baseline to 69.0 (SD, 21.4) on day 113; the functional scale and symptom scores (day 113) were higher than the baseline scores (P <.05) for EORTC Social Functioning. The FACT-Bl total, BLCS, and TOI scores improved in 32.6%, 34.9%, and 32.6% of the patients by day 113; 26.3% to 37.8% of the patients exhibited improvements in EORTC QLQ-C30 functional scores. The best tumor shrinkage and posttreatment improvements in serum albumin and NLR correlated with increases in FACT-Bl total, TOI, and BLCS scores and in EORTC Physical Functioning and Role Functioning scores (P <.05). Conclusions: Durvalumab was associated with improvements in disease-related symptoms, functioning, and HRQOL in patients with mUC. Improvements in systemic inflammation may contribute to PRO improvements in these patients.
KW - biomarkers
KW - durvalumab
KW - health-related quality of life
KW - inflammation
KW - patient-reported outcome measures
KW - tumor
KW - urothelial carcinoma
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U2 - 10.1002/cncr.32532
DO - 10.1002/cncr.32532
M3 - Article
C2 - 31581306
AN - SCOPUS:85073931367
SN - 0008-543X
VL - 126
SP - 432
EP - 443
JO - Cancer
JF - Cancer
IS - 2
ER -