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

Figures & data

Table 1 Publications of completed clinical studies about treatment with cabozantinib in first-line setting for advanced renal cell carcinoma patients

Author and year	Study type	Type of patients	Phase	Comparators	Number of patients and/or studies	Primary end point	Secondary end points	Outcomes in favor of cabozantiniba
Choueiri et al, 2017^Citation12	Randomized multicenter trial	Naïve, intermediate, and poor risk	II	Sunitinib	157	PFS	ORR, OS, safety	PFS, ORR
Choueiri et al, 2018^Citation17	Update and IRC assessment of a randomized trial	Naïve, intermediate, and poor risk	II	Sunitinib	156b	PFS	ORR, OS, safety	PFS, ORR
George et al, 2018^Citation18	Subgroup analyses of a randomized trial	Naïve, intermediate, and poor risk	II	Sunitinib	157	PFS basing on IMDC risk group, bone metastases, age, sex, ECOG PS, MET status	ORR basing on IMDC risk group, bone metastases, age, sex, ECOG PS, MET status	PFS and ORR in all subgroups
Feldman et al, 2018^Citation19	HRQoL post hoc analysis of a randomized trial	Naïve, intermediate, and poor risk	II	Sunitinib	157	ECOG PS score pre- and post- PD	ECOG score deterioration	–
Chen et al, 2018^Citation20	Q-TWiST post hoc analysis of a randomized trial	Naïve, intermediate, and poor risk	II	Sunitinib	157	Q-TWiST	–	NAc
Schmidt et al, 2018^Citation21	Network meta-analysis	Favorable, intermediate, and poor risk	NA	Sunitinib, sorafenib, IFN, bevacizumab plus IFN, temsirolimus	13	PFS	OS	PFS
Wallis et al, 2018^Citation22	Network meta-analysis	Favorable, intermediate, and poor risk	NA	NA Nivolumab plus ipilimumab, axitinib, sorafenib, sunitinib, atezolizumab plus bevacizumab	10 (4,819 patients)	PFS	OS, AEs	PFS

Notes:

a Only statistically significant differences were considered;

b one patient of 157 was not assessed by IRC;

c statistical significance not assessed (descriptive data favored cabozantinib for Q-TWiST).

Abbreviations: PFS, progression-free survival; ORR, objective response rate; OS, overall survival; IRC, independent radiologic review committee; IMDC, International Metastatic Renal Cell Carcinoma Database Consortium; HRQoL, health-related quality of life; PD, progression of disease; Q-TWiST, quality-adjusted time without symptoms of disease or toxicity of treatment; NA, not applicable; AEs, adverse events; ECOG, Eastern Cooperative Oncology Group; PS, performance status; IFN, interferon.

Figure 1 Flow diagram of the study selection.

Note: Duplicated excluded n=2.

Table 2 Trials in progress with the use of cabozantinib for previously untreated patients with advanced renal cancer

Trial number and/or name	Study type	Phase	Disease	Setting	Treatment arms	Estimated enrollment (No of patients)	Primary end point	Start date	Estimated completion date
NCT03170960^Citation23	Single-arm, dose-escalation	Ib-II	UC ccRCC NSCLC CRPC	First-line for ccRCC (expansion of cohort 1)	Cabozantinib plus atezolizumab	360 (total)	ORR (expansion of cohorts)	2017	2020
NCT03141177 CheckMate 9ER^Citation24	Multicenter, randomized, open-label	III	RCC with a clear- cell component	First-line	Nivolumab plus cabozantinib vs sunitinib	630	PFS	2017	2023
CABOPRE^Citation25	Multicenter, single-arm	II	RCC with a clear- cell component, suitable for CN	First-line	Cabozantinib for 12 weeks before CN and then until PD	50	ORR at 12 weeks	NA	NA
NCT02761057 PAPMET^Citation26	Multicenter, randomized	II	Papillary RCC	First- and second-line	Sunitinib vs cabozantinib vs crizotinib vs volitinib	180	PFS	2016	2020
NCT03354884 BONSAI^Citation27	Single-center, single-arm	II	Collecting ducts carcinoma	First-line	Cabozantinib	23	ORR	2018	2020
NCT03541902 CABOSUN II^Citation28	Multicenter, randomized	II	Variant histology RCC (papillary, chromophobe, Xp.11 translocation, undifferentiated, unclassified)	First-line	Cabozantinib vs sunitinib	84	PFS	2018	2020

Abbreviations: No, number; UC, urothelial carcinoma; ccRCC, clear-cell renal cell carcinoma; NSCLC, non-small-cell lung cancer; CRPC, castration-resistant prostate cancer; ORR, objective response rate; RCC, renal cell carcinoma; PFS, progression-free survival; CN, cytoreductive nephrectomy; PD, progression of disease; NA, not available.

ChoueiriTKHalabiSSanfordBLCabozantinib Versus Sunitinib As Initial Targeted Therapy for Patients With Metastatic Renal Cell Carcinoma of Poor or Intermediate Risk: The Alliance A031203 CABOSUN TrialJ Clin Oncol201735659159728199818

 PubMed Web of Science ®Google Scholar

ChoueiriTKHesselCHalabiSCabozantinib versus sunitinib as initial therapy for metastatic renal cell carcinoma of intermediate or poor risk (Alliance A031203 CABOSUN randomised trial): Progression- free survival by independent review and overall survival updateEur J Cancer201894e125

 Web of Science ®Google Scholar

GeorgeDJHesselCHalabiSCabozantinib versus sunitinib for previously untreated patients with advanced renal cell carcinoma (RCC) of intermediate or poor risk: Subgroup analysis of progression- free survival (PFS) and objective response rate (ORR) in the Alliance A031203 CABOSUN trialJ Clin Oncol201836Suppl 6582

 Web of Science ®Google Scholar

FeldmanDRFeullyMMengJECOG score analysis as a proxy for health-related quality of life assessment in patients with poor or intermediate risk metastatic renal cell carcinoma from the CABOSUN trial (Alliance A031203)J Clin Oncol20183615 Suppl

 Google Scholar

ChenRCFeullyMMengJQuality-adjusted time without symptoms or toxicity (Q-TWiST): Analysis of cabozantinib (Cabo) vs sunitinib (Sun) in patients with advanced renal cell carcinoma (aRCC) of intermediate or poor risk (Alliance A031203)J Clin Oncol201836Suppl abstr 4556

 Google Scholar

SchmidtEListerJNeumannMCabozantinib Versus Standard- of-Care Comparators in the Treatment of Advanced/Metastatic Renal Cell Carcinoma in Treatment-naïve Patients: a Systematic Review and Network Meta-AnalysisTarget Oncol20181320521629492762

 PubMed Web of Science ®Google Scholar

WallisCJDKlaassenZBhindiBFirst-line Systemic Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysisEur Urol Oncol2018743309321

 Google Scholar

Clinicaltrials.govStudy of cabozantinib in combination with atezolizumab to subjects with locally advanced or metastatic solid tumors [updated June 4, 2018; cited July 20, 2018]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03170960?term=NCT03170960&rank=1. NLM identifier: NCT03170960Accessed July 20, 2018

 Google Scholar

ChoueiriTKApoloAPowlesTEscudierBArenORShahAA phase 3, randomized, open-label study of nivolumab combined with cabozantinib vs sunitinib in patients with previously untreated advanced or metastatic renal cell carcinoma (RCC; CheckMate 9ER)J Clin Oncol201836Suppl abstr TPS4598

 Google Scholar

de VelascoGGonzálezBAlonsoTCABOPRE: Phase II study of cabozantinib prior to cytoreductive nephrectomy (CN) in locally advanced and/or metastatic renal cell carcinoma (mRCC)J Clin Oncol201836Suppl abstr TPS4603

 Google Scholar

Clinicaltrials.govCabozantinib S-malate, crizotinib, volitinib, or sunitinib malate in treating patients with locally advanced or metastatic kidney cancer [cited July 20, 2018]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02761057?term=NCT02761057&rank=1. NLM identifier: NCT02761057Accessed July 20, 2018

 Google Scholar

ProcopioGRattaRFucGA phase 2 study of cabozantinib as first-line treatment in collecting ducts renal cell carcinoma: The BONSAI trialJ Clin Oncol2018366 SupplTPS709

 Web of Science ®Google Scholar

Clinicaltrials.govCabozantinib Versus sunitinib for metastatic variant histology renal cell carcinoma [updated July 16, 2018; cited July 20, 2018]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT03541902?term=NCT03541902&rank=1. NLM identifier: NCT03541902Accessed July 20, 2018

 Google Scholar