Impact of first-line dual immuno-oncology combination therapy versus immuno-oncology plus tyrosine kinase inhibitor on outcomes of second-line VEGFR-TKI in advanced RCC: a real-world multi-institutional analysis.

[BACKGROUND] Data on the impact of first-line immune checkpoint inhibitor (ICI) combination therapy regimen on the outcomes of second-line tyrosine kinase inhibitor (TKI) treatment for advanced renal-cell carcinoma (RCC) remain limited.

[METHODS] We retrospectively evaluated data from 105 patients who discontinued first-line ICI combination therapy. Progression-free survival (PFS) after second-line TKI treatment and PFS2, defined as the sum of PFS during first-line and second-line therapies, were compared between patients who received dual ICI combination therapy (i.e., immunotherapy [IO]-IO) and those who received a combination of ICI and TKI (i.e., IO-TKI).

[RESULT] Of the 105 patients, 66 (63%) and 39 (37%) were treated with first-line IO-IO and IO-TKI combination therapy, respectively. The conversion rate to second-line therapy was higher in the IO-IO treatment group than in the IO-TKI group (73 vs. 54%, p = 0.0489). Sixty-six patients received second-line TKI treatment, and second-line PFS was longer in the IO-IO treatment group than in the IO-TKI group (median: 12.1 vs. 6.3 months, p = 0.0048). Additionally, PFS2 was longer in the IO-IO treatment group than in the IO-TKI group (median: 19.7 vs. 15.4 months, p = 0.0416). After adjusting for other covariates, the first-line treatment regimen (i.e., IO-IO vs. IO-TKI) was identified as an independent factor for PFS2 (HR: 0.51, p = 0.0057).

[CONCLUSION] This retrospective study using real-world data showed that second-line PFS and PFS2 were longer in patients treated with prior IO-IO combination therapy than in those treated with IO-TKI combination therapy.