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

Abstract

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.

Outcomes based on age in the phase III METEOR trial of cabozantinib versus everolimus in patients with advanced renal cell carcinoma

“…Patients were followed for OS every 8 weeks. Quality of Life (QoL) was measured using the validated patient self-reported questionnaire Functional Assessment of Cancer Therapy-Kidney Symptom Index-19 item (FKSI-19) as described [12].…”

“…The FKSI-19 questionnaire, which assesses disease-related symptoms, treatment side effects and function/well-being associated with advanced kidney cancer, was used to evaluate QoL in each of the subgroups [12]. Descriptive summaries of the FKSI-19 scores in each age subgroup are shown in Supplementary Fig.…”

“…1. A clinically relevant difference could not be shown between treatment groups in each age subgroup based on an effect size !0.30 from repeated measures analyses [12] ( Supplementary Table 5).…”

Cytoreductive nephrectomy is dead, long live cytoreductive nephrectomy

“…Specifically, the rate of grade 3–4 adverse events in the TKI treatment‐alone group was 42%, while this rate was only 33% in the TKI treatment plus CN group ( P = 0.04). Even when weighed against the reported 5.7% rate of Clavien–Dindo ≥3 surgical complications, the statistically significantly lower rate of adverse events for patients treated with surgery, undoubtedly related to the removal of the primary tumour, is not clinically negligible, given the need for multiple lines of medical therapy in intermediate‐ to poor‐risk mRCC . The benefits in terms of adverse events for patients who underwent CN were notable especially with regard to renal and urinary tract disorder (Table ).…”

Development of a Functional Assessment of Chronic Illness Therapy item library and primary symptom list for the assessment of patient-reported adverse events associated with immune checkpoint modulators

“…PROs are defined as "any report of the status of a patient's (or person's) health condition, health behavior, or experience with healthcare that comes directly from the patient, without interpretation of the patient's response by a clinician or anyone else" [17] . In clinical trials, PROs enhance understanding of treatment toxicity, HRQOL, and treatment value [18][19][20][21][22] . In clinical practice, PROs aid early symptom detection, symptom management, and treatment decision making [23][24][25][26][27] .…”