Survival outcomes of double- and triple-sequential targeted therapy in patients with metastatic renal cell carcinoma: a retrospective comparison

Objective To evaluate the progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with double- and triple-sequence targeted therapy (TT) using tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin inhibitors (mTORi). Materials and Methods Records of 292 patients with mRCC, treated with TT between January 2005 and July 2015, were analyzed retrospectively. Kaplan-Meier and log-rank analyses were used to calculate and compare the total PFS (tPFS) and OS when patients underwent double- or triple-TT using TKIs or mTORi. Results Eighty-one (27.7%) patients who underwent second-line TT were enrolled; 30 (10.3%) of whom underwent third-line TT. The tPFS and OS of double-TT using TKI-mTORi (5.4 and 30 months, respectively) were significantly better compared with TKI-TKI (0.3 and 2 months) or mTORi-TKI (2 and 6 months) (p <0.001). For triple-TT, the tPFS and OS of TKI-mTORi-TKI (22.8 and 25 months, respectively) were significantly superior compared with those for TKI-TKI-mTORi (4 and 9 months) (p <0.05).For patients with intermediate-risk according to the Heng or Memorial Sloan-Kettering Cancer Center risk models, TKI-mTORi was associated with a significantly longer tPFS and OS compared with TKI-TKI [expect for OS in the Heng group (p = 0.086)]. For the triple TT group, TKI-mTORi-TKI resulted in improved tPFS and OS compared with TKI-TKI-TKI or TKI-TKI-mTORi (p <0.05). Conclusion In patients with mRCC, sequential administration of TKI-mTORi led to a significantly superior tPFS compared with any other TT sequence. By contrast, OS did not differ significantly according to TT sequence.