Quality of life assessment in renal cell carcinoma Phase II and III clinical trials published between 2010 and 2020: a systematic review

2021 ◽  
Author(s):  
Alessandro Rizzo ◽  
Veronica Mollica ◽  
Filippo Gustavo Dall’Olio ◽  
Angela Dalia Ricci ◽  
Ilaria Maggio ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Life Assessment ◽  
Phase Iii ◽  
End Points

Aims: Quality of life (QoL) assessment is frequently not included among the end points of clinical trials (CTs) on renal cell carcinoma. Herein we aimed to describe the assessment and reporting of QoL in Phase II and Phase III CTs published between 2010 and 2020. Methods: A total of 25 CTs were included; 76% of trials included were conducted in metastatic renal cell carcinoma patients, while 20% of studies evaluated adjuvant systemic treatments. Results: In 13/25 publications, QoL was not listed among the end points, with secondary publications dedicated to QoL present in a minority of cases. Conclusions: QoL was not included among the end points of a large percentage of CTs. Implementing the inclusion of QoL represents an urgent need.

scholarly journals PRISM protocol: a randomised phase II trial of nivolumab in combination with alternatively scheduled ipilimumab in first-line treatment of patients with advanced or metastatic renal cell carcinoma

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hannah L. Buckley ◽  
Fiona J. Collinson ◽  
Gemma Ainsworth ◽  
Heather Poad ◽  
Louise Flanagan ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Phase Iii ◽  
First Line ◽  
Grade 3

Abstract Background The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy. Methods The PRISM trial is a UK-based, open label, multi-centre, phase II, randomised controlled trial. The trial population consists of patients with untreated locally advanced or metastatic clear cell RCC, and aims to recruit 189 participants. Participants will be randomised on a 2:1 basis in favour of a modified schedule of 4 doses of 12-weekly ipilimumab versus a standard schedule of 4 doses of 3-weekly ipilimumab, both in combination with standard nivolumab. The proportion of participants experiencing a grade 3 or 4 adverse reaction within 12 months forms the primary endpoint of the study, but with 12-month progression free survival a key secondary endpoint. The incidence of all adverse events, discontinuation rates, overall response rate, duration of response, overall survival rates and health related quality of life will also be analysed as secondary endpoints. In addition, the potential of circulating and tissue-based biomarkers as predictors of therapy response will be explored. Discussion The combination of nivolumab with ipilimumab is active in patients with mRCC. Modifying the frequency of ipilimumab dosing may mitigate toxicity rates and positively impact quality of life without compromising efficacy, a hypothesis being explored in other tumour types such as non-small cell lung cancer. The best way to give this combination to patients with mRCC must be similarly established. Trial registration PRISM is registered with ISRCTN (reference ISRCTN95351638, 19/12/2017). Trial status At the time of submission, PRISM is open to recruitment and data collection is ongoing.

scholarly journals Quality of Life Outcomes for Cabozantinib Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma: METEOR Phase III Randomized Trial

2018 ◽  
Vol 36 (8) ◽  
pp. 757-764 ◽  
Author(s):  
David Cella ◽  
Bernard Escudier ◽  
Nizar M. Tannir ◽  
Thomas Powles ◽  
Frede Donskov ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Repeated Measures ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Renal Cell Carcinoma

Purpose In the phase III METEOR trial ( ClinicalTrials.gov identifier: NCT01865747), 658 previously treated patients with advanced renal cell carcinoma were randomly assigned 1:1 to receive cabozantinib or everolimus. The cabozantinib arm had improved progression-free survival, overall survival, and objective response rate compared with everolimus. Changes in quality of life (QoL), an exploratory end point, are reported here. Patients and Methods Patients completed the 19-item Functional Assessment of Cancer Therapy–Kidney Symptom Index (FKSI-19) and the five-level EuroQol (EQ-5D-5L) questionnaires at baseline and throughout the study. The nine-item FKSI–Disease-Related Symptoms (FKSI-DRS), a subset of FKSI-19, was also investigated. Data were summarized descriptively and by repeated-measures analysis (for which a clinically relevant difference was an effect size ≥ 0.3). Time to deterioration (TTD) was defined as the earlier of date of death, radiographic progressive disease, or ≥ 4-point decrease from baseline in FKSI-DRS. Results The QoL questionnaire completion rates remained ≥ 75% through week 48 in each arm. There was no difference over time for FKSI-19 Total, FKSI-DRS, or EQ-5D data between the cabozantinib and everolimus arms. Among the individual FKSI-19 items, cabozantinib was associated with worse diarrhea and nausea; everolimus was associated with worse shortness of breath. These differences are consistent with the adverse event profile of each drug. Cabozantinib improved TTD overall, with a marked improvement in patients with bone metastases at baseline. Conclusion In patients with advanced renal cell carcinoma, relative to everolimus, cabozantinib generally maintained QoL to a similar extent. Compared with everolimus, cabozantinib extended TTD overall and markedly improved TTD in patients with bone metastases.

Patient-reported outcomes in a randomized trial of everolimus with metastatic renal cell carcinoma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17516-e17516
Author(s):  
J. Beaumont ◽  
D. Cella ◽  
T. Hutson ◽  
S. Bracarda ◽  
V. Grünwald ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Patient Reported Outcomes ◽  
Phase Iii ◽  
Patient Reported ◽  
Secondary Analyses

e17516 Background: Patient-reported outcomes (PRO), including health-related quality of life (HRQL), were assessed in a Phase III trial of everolimus in metastatic renal cell carcinoma (mRCC) patients. Methods: Patients with mRCC were randomized (n=416) to receive everolimus or placebo plus best supportive care. Patients completed the FACT-Kidney Symptom Index- Disease Related Symptoms (FKSI-DRS) and EORTC-QLQ C30 at baseline and monthly during treatment. Karnofsky Performance Status (KPS) was also assessed at baseline and monthly during treatment. Primary analyses included time to deterioration defined as a decrease from baseline of at least 3 points for FKSI-DRS, at least 10% for EORTC Physical Function (PF) and Global Quality of Life (QL) scales, and at least 10 points for KPS. Secondary analyses considered tumor progressions that occurred prior to deterioration or censoring date as FKSI deterioration events and compared time to PRO deterioration by tumor progression. Comparisons were made using stratified log-rank tests and Cox proportional hazard models. Results: Time to deterioration in KPS was longer in the everolimus arm, and time to deterioration in FKSI-DRS was slightly longer ( Table ). There was no difference in time to deterioration in PF or QL. Secondary analyses showed median time to deterioration in FKSI-DRS was approximately doubled for the everolimus arm compared to placebo, and patients who progressed experienced a more rapid deterioration in FKSI-DRS and QL scores. Conclusions: Compared to placebo everolimus delayed progression of disease-related symptoms and KPS. No effect on time to deterioration of PF or QL could be determined. Secondary analyses suggest a delay in deterioration in kidney cancer related symptoms via tumor control. [Table: see text] [Table: see text]

Predicting survival in renal cell carcinoma: The role of quality-of-life assessment.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 460-460
Author(s):  
Digant Gupta ◽  
Donald Peter Braun ◽  
Christopher G. Lis ◽  
Edgar Donald Staren
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Significance ◽  
Life Assessment ◽  
Newly Diagnosed ◽  
Previously Treated Patients ◽  
Previously Treated

460 Background: Assessment of quality of life (QoL) with validated instruments has been increasing in the clinical oncology community, but to date few studies have examined its prognostic significance in renal cell carcinoma (RCC). We investigated the association between QoL at presentation and survival in RCC. Methods: A consecutive series of 138 RCC patients treated between January 2001 and December 2009. QoL was evaluated at baseline using EORTC-QLQ-C30 which incorporates 1 global, 5 functional and 8 symptom scales. Scores range from 0-100 with higher scores in the global/functional scales and lower scores in the symptom scales indicating better QoL. Patient survival was the primary endpoint. Cox regression was performed to evaluate the prognostic significance of QoL. Results: Mean age at diagnosis was 53.8 years. 51 patients were newly diagnosed at our hospital, while 87 were previously treated elsewhere. Stage at diagnosis was I, 32; II, 19; III, 32; and IV, 55. Median overall survival was 17.2 months (95% CI: 10.1-24.2 months). QoL scales predictive of survival upon univariate analysis were physical (p=0.003), role (p=0.02), social (p=0.03), fatigue (p=0.02), pain (p=0.03), and constipation (p=0.04). Upon multivariate analyses, after adjusting for age, gender, stage, and treatment history, physical (HR=0.89; 95% CI=0.78, 0.99; p=0.04), social (HR=0.91; 95% CI=0.83, 0.99; p=0.04), fatigue (HR=1.10; 95% CI=1.01, 1.19; p=0.03) and constipation (HR=1.11; 95% CI=1.02, 1.20; p=0.01) scales were significantly associated with survival, such that patients with higher (better) physical and social scores and lower (better) fatigue and constipation scores had better survival. For newly diagnosed patients, physical scale was significant, while for previously treated patients, physical, fatigue, and constipation scales were significant. Conclusions: Baseline QoL elements that reflect specific functional and symptomatic attributes provide useful prognostic information in RCC. Significantly, this held true for physical function for both newly diagnosed and previously treated patients. Such determinations should be considered when designing clinical trials with survival endpoints and may aid decision-making in clinical practice.

Correlation between patient-reported fatigue and hemoglobin (Hgb) levels in metastatic renal cell carcinoma (mRCC) patients (pts) receiving sunitinib (SU).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 418-418
Author(s):  
Mellar P. Davis ◽  
Ewa M. Matczak ◽  
Connie Chen ◽  
Beata Korytowsky ◽  
Helen Bhattacharyya ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Clinical Trials ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Dosing Schedule ◽  
Patient Reported ◽  
The Relationship

418 Background: Low Hgb is linked with fatigue in cancer pts; however, the onset and severity of fatigue is multifactorial. The approved SU dosing schedule in mRCC is 4 weeks on treatment, 2 weeks off, and quality of life (QoL) when examined on day 28 is significantly worse than on day 1 of each cycle. The relationship between pt-reported fatigue and Hgb levels with SU in mRCC was investigated. Methods: Two randomized clinical trials of SU were combined to examine the pt-reported fatigue item from FKSI-15 which asks pts to indicate their level of fatigue on a 5-point Likert scale from 0=“not at all” to 4=“very much”. Data were collected at baseline (BL; cycle 1, day 1) and on days 28 and 42 of each 42-day cycle. For each visit, only pts who had data for both fatigue and Hgb at BL were included in the analysis. Results: 481 pts were included. Fatigue and Hgb levels at BL and over cycles 1–6 are shown in the table. Pts reported worse fatigue (higher score) at day 28 of each cycle than on day 42. Fatigue scores typically ranged from 1= “a little bit” to 2=“somewhat”. Changes in Hgb levels, however, were modest and opposite to fatigue changes i.e. were higher on day 28 of each cycle and lower on day 42. Findings were similar beyond cycle 6. Conclusions: Pts indicated less fatigue on day 42, after the 2-week break, than on day 28 of each cycle, consistent with previous overall QoL findings. Low Hgb is not associated with worse fatigue in mRCC pts receiving SU.This may be due to the multifactorial nature of fatigue. The ‘on’ and ‘off’ periods in intermittent dosing are important considerations of patients’ full experience of QoL. [Table: see text]

Phase II trial of neoadjuvant axitinib in patients with locally advanced nonmetastatic clear cell renal cell carcinoma.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 441-441
Author(s):  
Jose A. Karam ◽  
Catherine E Devine ◽  
Diana L Urbauer ◽  
Marisa Lozano ◽  
Kamran Ahrar ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Phase Ii ◽  
Renal Cell ◽  
Clear Cell ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Cell Renal Cell Carcinoma

441^ Background: Previous studies have shown minimal impact of tyrosine kinase inhibitors on primary renal tumors. In this phase II trial, we investigate the safety and role of the axitinib in downsizing tumors in patients with non-metastatic clear cell renal cell carcinoma (RCC) prior to surgical resection. Methods: Patients with clinical stage T2-T3b N0 M0 biopsy-proven RCC were eligible for this study. Patients received axitinib daily for 12 weeks prior to surgery. The primary outcome was objective response rate. Secondary outcomes included safety, tolerability, feasibility of administration of axitinib and quality of life (using FKSI-15). A dedicated radiologist independently reviewed all CT scans to evaluate for response using RECIST. Results: Twenty-four patients were treated between 2011 and 2013. All patients had biopsy-proven clear cell RCC. Twenty-three patients continued axitinib for 12 weeks, and underwent surgery as planned without delay. One patient stopped treatment before 12 weeks due to adverse events (AEs) and was taken to surgery early. Median reduction of primary renal tumor size was 28.3% (range 5.3-42.9%). Eleven patients (45.8%) experienced a partial response by RECIST, and 13 patients had stable disease. There was no progression of disease while on axitinib. The most common AEs were hypertension, fatigue, oral mucositis, hypothyroidism, and hand-foot syndrome. No grade 4 AEs were observed. Intraoperatively, no complications or unusual bleeding were encountered. Postoperatively, 2 grade 3 and 13 grade 2 complications were noted, while no grade 4 or 5 complications occurred. FKSI-15 did change over time (p < 0.0001), with quality of life worsening in comparison to the screening assessment by week 7 (p = 0.0004). However, by week 19, quality of life was not found to be statistically different from screening (p = 0.3344). Conclusions: Axitinib was clinically active and well tolerated in the neoadjuvant setting in patients with locally advanced non-metastatic ccRCC. Clinical trial information: NCT01263769.

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