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.

Fig 1.

Patient disposition (intent-to-treat population). Baseline FKSI-19 (EQ-5D-5L) data were available for 324 (323) patients in the cabozantinib arm and 313 (314) patients in the everolimus arm, of whom 319 (317) and 303 (304), respectively, had at least one postbaseline assessment. (*) Five patients randomly assigned to the everolimus arm did not receive study treatment. In addition, one patient randomly assigned to the everolimus arm received cabozantinib as study treatment. (†) Includes withdrawals, protocol deviations, lack of efficacy, investigator decision. EQ-5D-5L, five-level EuroQol questionnaire; FKSI-19, 19-item Functional Assessment of Cancer Therapy–Kidney Symptom Index; ITT, intent to treat; QoL, quality of life.

Fig 2.

Plot of absolute FKSI scores over time (intent-to-treat population). (A) FKSI-19 Total. (B) Nine-item FKSI-DRS. DRS, Disease-Related Symptoms; FKSI, Functional Assessment of Cancer Therapy–Kidney Symptom Index; PD, progressive disease; rPD, radiographic progressive disease; TRT, treatment; QoL, quality of life; W, week. Higher scores indicate improved QoL status. Peri Last Dose is the closest QoL assessment 2 weeks before to 4 weeks after last dose. Peri rPD per Inv is the closest QoL assessment 2 weeks before to 4 weeks after first date of PD per investigator.

Fig 3.

Effect of baseline FKSI-DRS on OS (intent-to-treat population). DRS, Disease-Related Symptoms; FKSI, Functional Assessment of Cancer Therapy–Kidney Symptom Index; HR, hazard ratio; mo, month; OS, overall survival; QoL, quality of life.