Cabozantinib Versus Standard-of-Care Comparators in the Treatment of Advanced/Metastatic Renal Cell Carcinoma in Treatment-naïve Patients: a Systematic Review and Network Meta-Analysis

Abstract

BackgroundCabozantinib has recently been evaluated as a first-line treatment in advanced renal cell carcinoma (aRCC).ObjectiveTo indirectly assess efficacy of cabozantinib versus standard-of-care (SoC) comparators in the first-line treatment of aRCC.MethodsWe conducted a systematic literature review (SLR) to identify randomized controlled studies in the first-line setting for aRCC. The outcomes analyzed were overall survival (OS) and progression-free survival (PFS). A network meta-analysis (NMA) was conducted comparing OS and PFS hazard ratios (HRs).ResultsThirteen studies were identified in the SLR to be eligible for inclusion in the NMA. The overall study populations were heterogeneous in terms of risk groups; some studies included favorable risk patients. In intermediate-risk patients, HRs (95% confidence interval) for PFS were 0.52 (0.33, 0.82), 0.46 (0.26, 0.80), 0.20 (0.12, 0.36), and 0.37 (0.20, 0.68) when cabozantinib was compared with sunitinib, sorafenib, interferon (IFN), or bevacizumab plus IFN, respectively. In poor-risk patients, the NMA also demonstrated significant superiority in terms of PFS for cabozantinib; HRs were 0.31 (0.11, 0.90), 0.22 (0.06, 0.87), 0.16 (0.04, 0.64), and 0.20 (0.05, 0.88), when cabozantinib was compared with sunitinib, temsirolimus, IFN, or bevacizumab plus IFN, respectively. When the overall study populations were compared, the results were similar to the subgroup analyses. OS HRs in all analyses favored cabozantinib, but were not statistically significant.ConclusionsThe results suggest that cabozantinib significantly increases PFS in intermediate-, and poor-risk subgroups when compared to standard-of-care comparators. Although overall populations included favorable risk patients in some studies, the results seen were consistent with the subgroup analyses.Electronic supplementary materialThe online version of this article (10.1007/s11523-018-0559-0) contains supplementary material, which is available to authorized users.

Spotlight on cabozantinib for previously untreated advanced renal cell carcinoma: evidence to date

“… 17 – 20 The other two reports included NMA of cabozantinib and its comparators in first- line setting for RCC patients. 21 , 22 Publications included in the review are presented in Table 1 .…”

“…The first, by Schmidt et al, directly compares cabozantinib with other first-line standard-of-care drugs, such as sunitinib, sorafenib, temsirolimus, interferon (IFN), or bevacizumab plus IFN, respectively. 21 The NMA included 13 trials; considering that the unique clinical trial with cabozantinib in this setting enrolled only poor- and intermediate-risk patients, while other studies used in this NMA also included favorable-risk cases, both the overall study populations and the subgroup of interest were explored. In either case, cabozantinib provided longer PFS than all alternative therapies, while the improvement in OS was not statistically significant.…”

“…The authors concluded that cabozantinib is a promising first-line treatment for mRCC compared to available standard-of-care options, with clinical implications for intermediate- and poor-risk patients. 21 …”

“… 12 , 17 The NMA comparing this drug to other TKIs used today for untreated mRCC patients, as well as to the new treatment options with CKIs, confirmed that cabozantinib could represent the best choice for PFS, with non-significant penalty in terms of OS. 21 , 22 Finally, the subgroup analyses of the treated population suggest that a biomarker-driven approach, using MET expression to select patients for treatment, may potentially strengthen the outcomes of treatment with this drug. 18 …”

Cabozantinib as first-line treatment in advanced renal cell carcinoma: a profile of its use

“…Recent network meta-analyses (NMAs) [ 25 , 26 ] have evaluated the efficacy of first-line treatments for mRCC/aRCC. One NMA investigated cabozantinib versus standard-of-care options in the first-line treatment of mRCC/aRCC based on IMDC risk [ 25 ].…”