In the oncology setting, patient-reported outcome measures (PROMs) provide important data that help to ensure patient-relevant endpoints are captured and reported. Use of this information for treatment decision-making by clinicians and patients in real-world settings is facilitated by consistent and transparent reporting of trial methods.
Objective
To identify and compare PROMs used in advanced renal cell carcinoma (RCC) trials in terms of the rationale for the choice of measure, endpoint hierarchy (primary, secondary, exploratory), assessment time points, statistical methods, and statistical metrics for interpretation.
Evidence acquisition
A systematic literature review via searches of four online databases (2016–2021) and recent conference abstracts (2019–2021) identified 2616 articles, of which 33 were included in the review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.
Evidence synthesis
Among the 33 clinical studies included, 19 different PROMs were identified: three kidney cancer–specific scales, two cancer-specific scales, two generic scales, and 12 symptom-specific scales. The endpoint hierarchy for patient reported outcome (PRO) assessment was reported in 42% of the studies; one study included PROs as a primary endpoint. Reporting of time points, minimal important differences, and statistical analyses was highly heterogeneous.
Conclusions
A diverse range of PROMs have been included in clinical studies for patients with advanced/metastatic RCC. Prespecified analyses for PRO assessments were generally not stated, while analytical methods and reporting varied. An improvement in alignment across studies would better inform regulatory, market-access, reimbursement, and clinical decision-making to improve patient care.
Motzer and colleagues recently published in European Urology a systematic literature review aimed at identifying and comparing the patient-reported outcome measurements (PROMs) used in clinical trials investigating systemic treatments for locally-advanced and/or metastatic renal cell carcinoma (RCC) [1].
They retrieved 33 studies of interest, and identified 19 different PROMs, namely three kidney cancer–specific scales, two cancer-specific scales, two generic scales, and 12 symptom-specific scales.
With their effort, the authors observed a relatively low prevalence of patient-reported data in the field of RCC. Out of more than 2,600 abstracts screened, only 33 studies (<1.3%) included patient-reported outcome measures (PROMs).
Secondly, the review underlined that a diverse range of PROMs is included in clinical studies for patients with locally-advanced and/or metastatic RCC. Moreover, the endpoint hierarchy for patient-reported outcome assessment was reported by < 50% of the studies, with only one study including PROMs as a primary endpoint. Finally, the majority of the studies retrieved did not state prespecified analyses for patient-reported outcomes.
The above mentioned article is addressing an important lack in the field. It is crucial to raise the awareness how few clinical trials for kidney cancer are assessing the impact of cancer therapies on health outcomes from the patient’s perspective.
The issue of the heterogeneity in the choice of the PROMs across the studies may be explained by the different stages of enrolled “diseases”, and the different pharmacology of the treatment investigated with its relative expected toxicity profile. For instance, compared to trials investigating on targeted therapies, the assessment of the impact on PROMs by immune-checkpoint inhibitors will require the validation of additional questionnaires.
An evident limitation of the studies about the topic is the lack of explanations why and how a given patient-reported outcome is selected to be the PROMs in a specific study. Indeed, the rationale for selection and the selection process are rarely reported.
In summary, it is key to promote patient centricity in clinical trials. For example, the improvement in progression-free survival observed with triplet therapy (cabozantinib + nivolumab and ipilimumab) in the COSMIC-313 trial came with trade-off adverse events that undoubtedly significantly impaired patients’ quality of life: as such, higher Grade 3-4 adverse events were experienced by patients receiving triplet therapy (79% vs 56%) [2]. In such a trial, the assessment of PROMs is at least equally important to survival analysis. Thus, depending on the various outcome measures analysed in the trial, the “positivity” of its results may vary.
The improvement in alignment across studies in the field will foster better regulatory, market-access, reimbursement, and clinical decision-making, with improvement in patient care.
References
Motzer RJ, Rane PP, Saretsky TL, et al. Patient-reported Outcome Measurement and Reporting for Patients with Advanced Renal Cell Carcinoma: A Systematic Literature Review. Eur Urol. 2023 Aug 5:S0302-2838(23)02971-8. doi: 10.1016/j.eururo.2023.07.006. Epub ahead of print.
Choueiri TK, Powles T, Albiges L, et al. COSMIC-313 Investigators. Cabozantinib plus Nivolumab and Ipilimumab in Renal-Cell Carcinoma. N Engl J Med. 2023 May 11;388(19):1767-1778. doi: 10.1056/NEJMoa2212851.