Second-line tyrosine kinase inhibitor-therapy after immunotherapy-failure

Most contemporary metastatic renal-cell carcinoma patients receive first-line immunotherapy and tyrosine kinase inhibitor (TKI) combination or immunotherapy-immunotherapy combination, as first-line standards of care. However, second-line therapy choices are less well established. To address this void, we examined existing evidence supporting second and subsequent-line treatment options after immunotherapy-based combination therapy.

Evidence regarding efficacy of second-line therapy after immunotherapy-based combination is mainly retrospective, except for axitinib, which is the only TKI with prospective efficacy data in this setting. Cabozantinib demonstrated excellent second-line progression-free survival (PFS) that remained in third or later line use, albeit based on small numbers of observations. Moreover, pazopanib demonstrated excellent PFS, but showed wider variability in PFS rates. Sunitinib's PFS rates appeared lower than for axitinib, cabozantinib or pazopanib. Finally, inhibitors of the mammalian target of rapamycin pathway appeared to offer even lower efficacy than any TKI after immunotherapy-based therapy combinations.

All available contemporary evidence about TKI efficacy after immunotherapy-based therapy combinations is based on institutional studies. No major differences in efficacy for the examined TKIs after immunotherapy-based combination therapies were recorded. In general, these showed similar efficacy to their efficacy data recorded in first-line.