Metastatic renal cell carcinoma in the METEOR trial: cabozantinib vs everolimus

A recent phase 3 study showed that cabozantinib had an advantage in progression-free survival (PFS), overall survival (OS), and improved time to deterioration (TDD) when compared to everolimus for treatment of advanced renal cell carcinoma (RCC). Both treatments gave patients a similar quality of life (QoL). The findings were published in the Journal of Clinical Oncology.

The METEOR trial was an open-label study that included 658 patients with advanced or metastatic clear cell RCC from 26 countries. Patients were randomized to receive oral cabozantinib 60 mg daily or everolimus 10 mg daily.

Participants received at least one previous treatment with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFR-TKI) with disease progression. A primary end point of the study was PFS, and secondary end points included OS and objective response rate (ORR). The safety and efficacy results of the METEOR trial were previously published.¹

In this study, a group of investigators led by David Cella, PhD, from the Northwestern University Feinberg School of Medicine in Chicago, IL, assessed changes in QoL from baseline, which was an exploratory endpoint.

“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,” concluded the authors.

Cabozantinib is an oral inhibitor of TKIs, including VEGFR, MET, and AXL. Upregulation of MET and AXL genes in clear cell RCC has been implicated in tumor progression and VEGFR-TKI resistance. It is associated with a poor prognosis.

To evaluate QoL, patients completed the Functional Assessment of Cancer Therapy—Kidney Symptoms Index-19 item (FKSI-19) and the EuroQol Group’s five-level (EQ-5D-5L) questionnaires at baseline, every four weeks through week 25, then every eight weeks for the first year, and then every 12 weeks.

The FKSI-19 assesses the severity and interference in activity of disease-related symptoms (DRS) both physical and emotional, treatment side effects, as well as function and well-being in advanced RCC. Each item is scored based on symptom severity and interference on activity on a scale of 0 (none) to 4 (very much). A nine-item DRS version, FKSI-DRS, was also evaluated.

The EQ-5D-5L is a standardized measure of health status and comprises five functional and symptom dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. For each dimension, patients indicate health status scoring from level 1 (no problem) to 5 (extreme problem).

Patients also completed a visual analog scale (EQ-VAS) ranging from “worst health you can imagine” to “best health you can imagine.”

A post hoc analysis analyzed time to deterioration (TTD) which was defined as the earlier of the following: date of death, radiographic disease progression (rPD), or a decrease from baseline of at least 4 points on the FKSI-DRS.

Another post-hoc analysis evaluated the effect of FKSI-DRS scores on OS between the treatment groups.

In general, baseline characteristics were similar in each arm of the study; the mean age was 62 years, the majority of participants were men, and questionnaire completion rates were high and similar in both groups.

Overall, no differences over time were reported between the treatment groups on the basis of descriptive summaries for the FKSI-19, the FKSI-DRS, or for the EQ-VAS. Among the 19 items on the FKSI-19, the only differences were lower scores in the cabozantinib arm for diarrhea and nausea, and lower scores in the everolimus arm for shortness of breath. Similarly, there were no differences over time between the treatment arms for the EQ-Index.

At the time of rPD, there was a notable decrease in QoL scores compared with baseline. Progressive disease was the most frequent reason for study discontinuation. Cabozantinib treatment improved TTD compared to everolimus (median TTD, 5.5 vs 3.7 months, respectively).

In a subgroup analysis of patients with bone metastases, the investigators noted a marked TTD improvement with cabozantinib treatment compared to everolimus (median TTD, 5.6 vs 1.9 months, respectively).

Baseline FKSI-DRS scores higher than the median population values were associated with improved OS in both treatment groups.

“The METEOR trial showed that QoL declined initially and was generally maintained over time to a similar extent in both the cabozantinib and everolimus arms. The totality of results (including PFS, OS, and ORR) shows that cabozantinib has a favorable clinical benefit compared to everolimus for previously treated patients with advanced RCC,” the researchers concluded.

To read more about this study, click here. 

Reference:

1. Choueiri TK, et al. Lancet Oncol. 2016 Jul;17(7):917-927.