Outcomes of systemic targeted therapy in recurrent renal cell carcinoma treated with adjuvant sunitinib

Abstract

To assess the efficacy and tolerability of rechallenge with sunitinib and other targeted therapies (TTs) in patitents with relapsed recurrent renal cell carcinoma (RCC) in the advanced setting. MethodsIn this multi-institutional retrospective study, patients with relapsed RCC were rechallenged with sunitinib or other systemic TTs as a first-line therapeutic approach after failed adjuvant sunitinib treatment. Patient characteristics, treatments and clinical outcomes were recorded. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR) and overall survival (OS). ResultsA total of 34 patients with relapses were recorded, and 25 of these (73.5%) were men. Twenty-five patients were treated with systemic TT: 65% of patients received TT against the vascular endothelial growth factor pathway (including sunitinib), 21.7% received mammalian target of rapamycin inhibitors and 13% received immunotherapy. The median (interquartile range) time to relapse was 20.3 (5.2-20.4) months from diagnosis, and 7.5 months (1.0-8.5) from the end of adjuvant suntinib treatment. At a median follow-up of 23.5 months, 24 of the 25 patients had progressed on first-line systemic therapy. The median PFS was 12.0 months (95% confidence interval [CI] 5.78-18.2). There were no statistical differences in PFS between different treatments or sunitinib rechallenge. PFS was not statistically different in patients relapsing on or after adjuvant suntinib treatment (≤ 6 or >6 months after adjuvant suntinib ending). The ORR was 20.5%. The median OS was 29.1 months (95% CI 16.4-41.8). ConclusionsRechallenge with sunitinib or other systemic therapies is still a feasible therapeutic option that provides patients with advanced or metastastic RCC with additional clinical benefits with regard to PFS and OS after failed response to adjuvant sunitinib.

Rationale for immune checkpoint inhibitors plus targeted therapy for advanced renal cell carcinoma

“…The 25 patients were treated with targeted therapies again (including sunitinib) after they were diagnosed with recurrence of RCC, of which 24 showed progress in treatment. The PFS was 12 months (95% CI, 5.78–18.2), the median OS was 29.1 months (95% CI, 16.4–41.8), and the ORR was 20.5% [ 139 ].…”

Comparison of tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma with rhabdoid and sarcomatoid differentiations

“…For a long time, TKIs were the first‐line treatment option for metastatic RCC (mRCC). Updated clinical guidelines continue to advocate the sequential application of various antiangiogenic targeted medicines as the second and subsequent lines of therapy for mRCC, despite the use of immune checkpoint inhibitors (ICIs) having raised concerns in recent years 8 . Of the TKIs, sunitinib and pazopanib are the first‐line drugs of choice for the treatment of mRCC.…”

“…Updated clinical guidelines continue to advocate the sequential application of various antiangiogenic targeted medicines as the second and subsequent lines of therapy for mRCC, despite the use of immune checkpoint inhibitors (ICIs) having raised concerns in recent years. 8 Of the TKIs, sunitinib and pazopanib are the first‐line drugs of choice for the treatment of mRCC. A phase III trial conducted by Sternberg et al 9 evaluated the efficacy and safety of pazopanib and found that progression‐free survival (PFS) and tumor response significantly increased after pazopanib treatment in treatment‐naive and cytokine‐pretreated patients with advanced and/or mRCC compared to those in placebo‐controlled patients.…”