Subsequent systemic therapy initiation after first-line discontinuation in metastatic renal cell carcinoma: insights from a Japanese real-world cohort

Background Sequential systemic therapy after first-line discontinuation in metastatic renal cell carcinoma remains incompletely characterized in routine practice. We aimed to evaluate subsequent systemic therapy initiation in a Japanese real-world cohort and identify clinical factors associated with failure to initiate subsequent therapy. Patients and methods The primary analysis used real-world data from the Japanese AGEHA database ( n = 518). In the real-world cohort, patient flow after first-line treatment was described, and subsequent systemic therapy initiation was evaluated primarily among patients with discontinuation due to progressive disease (PD) or adverse events (AEs). Multivariable logistic regression was carried out to identify factors associated with failure to initiate subsequent therapy. Results Among patients with PD- or AE-related discontinuation, subsequent systemic therapy was initiated in 66.7% of those receiving first-line tyrosine kinase inhibitor (TKI) monotherapy and 59.9% of those receiving immune-oncology (IO)-based regimens. Failure to initiate subsequent therapy was independently associated with poorer Eastern Cooperative Oncology Group performance status and receipt of IO-based first-line regimens, whereas discontinuation due to PD was associated with a higher likelihood of subsequent therapy initiation. Conclusions Failure to initiate subsequent therapy after first-line discontinuation was not uncommon in real-world practice, but its interpretation depended on the denominator definition and treatment context. In the immune checkpoint inhibitor era, lower rates of subsequent therapy initiation may not have the same clinical implications as in the TKI monotherapy era and should be interpreted cautiously.