Axitinib and Cabozantinib in the treatment of sunitinib-refractory patients with metastatic renal cell carcinoma (mRCC): Results of matching adjusted indirect treatment comparison (MAIC) analysis of AXIS and METEOR trials

Axitinib and Cabozantinib are approved 2^nd-line targeted agents frequently used to treat metastatic renal cell carcinoma (mRCC); however, there are no head-to-head trials that compare the relative efficacy of these agents. As baseline characteristics are different between AXIS and METEOR, most notably a significantly higher share of poor risk patients are in AXIS, naïve comparisons are not suitable. The objective of this study was to compare outcomes in sunitinib-refractory (su-r) mRCC patients treated with axitinib or cabozantinib using a methodology to conduct indirect treatment comparison.

A matching adjusted indirect comparison (MAIC), which adjusts for imbalances in baseline characteristics between trials, was conducted to compare progression-free survival (PFS) and overall survival (OS) in sunitinib-refractory patients. Individual patient-level data from the sunitinib-refractory axitinib arm of the AXIS trial were weighted to match published patient characteristics of the cabozantinib arm from the METEOR trial to conduct an indirect comparison. Since Karnofsky performance score (KPS) was not collected in AXIS, a conversion from Eastern Cooperative Oncology Group (ECOG) performance status was done to derive Memorial Sloan Kettering Cancer Center (MSKCC) score in order to compare patient prognosis between AXIS and METEOR. To assess sensitivity of these results, an alternative mapping was also performed to derive MSKCC score and sensitivity analyses conducted.

After matching, baseline characteristics were balanced between axitinib and cabozantinib patients. No statistical difference was found in the estimated median (m) PFS (mPFS= 7.8 and 9.1 months) and mOS (mOS= 23.8 and 21.4 months) between axitinib and cabozantinib, respectively. In sensitivity analysis, fewer AXIS patients fell into the MSKCC poor risk category and the estimated treatment effect for both PFS and OS trended towards favoring cabozantinib; however, these results were also not statistically significant.

This analysis suggests no evidence of a statistically significant difference in PFS and OS between axitinib and cabozantinib in sunitinib-refractory mRCC patients after adjustment for differences in baseline characteristics. OS analyses could not account for likely imbalance in subsequent treatments.