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

Abstract

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.

Keywords: cabozantinib; dose intensity; immuno-oncology; immunotherapy; kidney cancer; nivolumab; relative dose intensity.