Impact of starting dose of tyrosine kinase inhibitors on outcomes following combination therapy of immune checkpoint inhibitors with tyrosine kinase inhibitors for previously untreated advanced renal cell carcinoma

Background The impact of the starting dose of tyrosine kinase inhibitors (TKIs) following combination therapy of immune checkpoint inhibitors with TKIs (i.e. IO–TKI) for advanced renal cell carcinoma (RCC) remains unclear. Methods We retrospectively evaluated clinical data from 155 patients treated with first-line IO–TKI for RCC. Patients were categorized into full-dose and reduced-dose groups based on their starting dose of TKIs. Effectiveness and safety profiles were compared between groups. Results A reduced starting dose was administered to 52 patients (34%). These patients were older (P = 0.0137) and received pembrolizumab plus axitinib more frequently, while lenvatinib plus pembrolizumab was less used (P = 0.0258) compared to the full-dose group. Progression-free survival and overall survival did not significantly differ between the full-dose and reduced-dose groups (P = 0.202 and P = 0.309, respectively). Although the objective response rate appeared higher in the full-dose group, the difference was not statistically significant after adjusting for other covariates (P = 0.0588). Safety profiles were comparable, with no significant differences in TKI dose reduction, drug interruption or discontinuation, or glucocorticoids use (P > 0.05). However, adverse events of grade ≥3 were more frequent in the full-dose group, although not statistically significant (P = 0.121). Conclusion The starting dose of TKIs did not significantly impact clinical outcomes following IO–TKI for RCC. These findings suggest a potential for the optimization of the starting dose of TKIs; however, prospective studies are warranted to confirm these findings.