Discussion
cancer, HGF
CANCER
This study was conducted to bridge the results of the cabozantinib arm in the METEOR trial to Japanese patients with a reasonable sample size set for statistical evaluation of IRC-assessed ORR. Support for the long-term efficacy and safety findings for cabozantinib in Japanese patients with ccRCC who had received at least one prior VEGFR-TKI was shown. The IRC-assessed ORR (25.7% [90% CI 14.1–40.6]) and median PFS (11.1 months [95% CI 7.4–18.4]) were numerically higher than those of the cabozantinib arm (Almost half of the enrolled patients (15/35, 42.9%) had received IO agents with or without a TKI before starting the study protocol. IO agents have been evolving the treatment of cancer worldwide since the approval of the ipilimumab in 2011 [Predictive biomarkers associated with cabozantinib treatment responses will support the identification of patients who may benefit from treatment. Currently, no plasma biomarkers that are consistently predictive or prognostic for an improved benefit with cabozantinib treatment have been found. For example, on-treatment changes in HGF appeared prognostic for improved PFS or OS with cabozantinib in univariate analyses, but not independently prognostic in multivariate analyses in the METEOR trial [In our study described here, an exploratory examination of four potential biomarkers suggested in the METEOR trial was undertaken using ELISA and plasma samples, which is a feasible method in clinical practice. Plasma levels of MET and AXL, which are membrane receptors, were assessed as surrogate markers for these receptors. Fold changes from baseline in the median/mean at week 5 were similar to the results in the cabozantinib arm of the METEOR trial [Tanimoto et al., previously reported that serum HGF levels were significantly higher in patients with ccRCC (1070.7 pg/mL, In summary, support for the long-term efficacy and safety findings for cabozantinib in Japanese patients with ccRCC who had received at least one prior VEGFR-TKI was shown in our study. Responders tended to show lower baseline HGF levels.