CABOSEQ: The Effectiveness of Cabozantinib in Patients With Treatment Refractory Advanced Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)

Navani, Vishal; Wells, J.C.; Boyne, Devon J.; Cheung, Winson Y.; Brenner, Darren M.; McGregor, Bradley A.; Labaki, Chris; Schmidt, Andrew; McKay, Rana R.; Meza, Luís; Pal, Sumanta K.; Donskov, Frede; Beuselinck, Benoît; Otiato, Maxwell; Ludwig, Lisa; Powles, Thomas; Szabados, Bernadett; Choueiri, Toni K.; Heng, Daniel Y.C.

doi:10.1016/j.clgc.2022.07.008

Cited by 13 publications

(9 citation statements)

References 24 publications

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“…Results of the CaboPoint study indicate better ORR in the TKI naïve group than the IOVE group (31.7% vs. 25%) [ 42 ]. In contrast, but consistent with our findings, the CABOSEQ study showed different results [ 26 ]. The best ORR occurred after IOVE treatment (32.5%).…”

Section: Discussionsupporting

confidence: 86%

“…The best ORR occurred after IOVE treatment (32.5%). Objective response rates after IOIO and pazopanib/sunitinib were comparable (26.4%; 25.2%) [ 26 ]. Moreover, the longest time to treatment failure (TTF) occurred after sunitinib/pazopanib in the first line.…”

Section: Discussionmentioning

confidence: 99%

“…However, statistical significance was not observed and Navani et al . concluded that there was comparable activity of 2L cabozantinib regardless of prior 1L therapy [ 26 ]. There might have been a bias due to the different characteristics of these groups.…”

Section: Discussionmentioning

confidence: 99%

“…Throughout the study, 11 patients (15%) received immunotherapy in previous lines of treatment (Tables 2-4), but only two patients (3%) received IOIO and none received IOVE, which are considered a current first-line treatment [19,20]. There is more and more evidence of cabozantinib efficacy after IOIO and IOVE [24][25][26][27]. The efficacy of cabozantinib after IOIO and IOVE is currently being researched [24][25][26][27].…”

Section: Discussionmentioning

confidence: 99%

“…Recent ESMO [19] and ASCO [20] guidelines recommend using IO combinations (IOIO) or IO-VEGFi combinations (IOVE) [21][22][23] as firstline treatment in advanced RCC. Despite the lack of goodquality evidence, some authors suggest that using cabozantinib after the failure of IO, IOIO, or IOVE is possible [24][25][26][27]. In the CABOSUN study cabozantinib demonstrated effectiveness as a first-line treatment in intermediate-and poor-risk patients according to International Metastatic RCC Database Consortium (IMDC) criteria [28,29].…”

Section: Introductionmentioning

confidence: 99%

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Activity of cabozantinib in further line treatment of metastatic clear cell renal cell carcinoma. Real-world experience in a single-center retrospective study

Domański,

Jarosińska,

Kruczyk

et al. 2023

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Introduction Cabozantinib is an oral inhibitor of MET, AXL, and vascular endothelial growth factor receptors. It has an immunomodulatory effect and may influence the tumor’s microenvironment and make mutated cells more sensitive to immune-mediated killing. These properties have made cabozantinib an effective drug for first-line or subsequent-line treatment after progression of metastatic renal cell carcinoma (mRCC), even after immunotherapy. Material and methods Seventy-one patients with mRCC were treated with second or further lines of cabozantinib at the Department of Genitourinary Oncology, Maria Sklodowska-Curie National Research Institute of Oncology. This study retrospectively evaluated the effectiveness of cabozantinib in subsequent lines of treatment. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints. The best overall response (BOR) to cabozantinib was the secondary endpoint. For this purpose, Cox’s proportional hazard model was used. Results The median PFS was 11 months (5; 23) and the median OS was 16 months (10; 42) and differed significantly in the second and further lines of treatment. Progression in the second and further lines was observed in 28 (93%) and 27 (66%) patients, respectively (p = 0.006). Partial response as the BOR was observed in one patient (3%) in the second line and 13 patients (32%) in the further lines (p = 0.012). Conclusions Cabozantinib has antitumor effects in the second and further lines of treatment. In this study we observed high efficiency of cabozantinib in further lines of treatment.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Activity of cabozantinib in further line treatment of metastatic clear cell renal cell carcinoma. Real-world experience in a single-center retrospective study

Domański,

Jarosińska,

Kruczyk

et al. 2023

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Identification of genomic drivers for the therapeutic response of Cabozantinib in patients with metastatic renal cell carcinoma

Borkowetz,

Sommer,

Baretton

et al. 2024

World J Urol

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Purpose Cabozantinib (CAB) as monotherapy or in combination with immune checkpoint inhibitors is used for systemic treatment of metastatic renal cell carcinoma (mRCC). However, little is known about predictors of treatment response to CAB. For this reason, known genomic drivers were examined to identify potential predictors of treatment response with CAB. Methods Twenty mRCC patients receiving monotherapy (≥ first-line) with CAB were prospectively included. DNA was extracted from archived primary tumors or metastatic tissue. Targeted DNA sequencing was performed using a gene panel including 328 genes (QIAseq Targeted DNA V3 Panel, Qiagen). The variant evaluation was performed using Varsome. The endpoints were treatment-failure-free-survival (TFFS) to CAB. Results 26% of patients received systemic RCC treatment as the primary option. Six patients were treated with CAB in first-line (1L) and 12 patients in ≥ 2L. The median follow-up after initiation of systemic treatment was 26.7 months (mo). The PBRM1 (7 alleles), SETD2 (7 alleles), VHL (11 alleles), and CHEK2 (14 alleles) genes were most frequently altered. The median time to TFFS was 10.5 mo (95% confidence interval (CI) 6.2–14.7 mo). There was a longer treatment response to CAB in patients with alterations of the SETD2 gene (SETD2 alteration median TFFS not reached vs. no SETD2 alterations 8.4 mo (95% CI 5.2–11.6 mo); p = 0.024). Conclusion Pathogenic variant genes may indicate treatment response to systemic therapy in mRCC. Patients with alterations of the SETD2 gene show longer responses to CAB treatment.

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Cabozantinib and Axitinib After Vascular Endothelial Growth Factor Therapy in Patients with Advanced Renal Cell Carcinoma: A Retrospective Cohort Study from England

Brown,

Harrow,

Marciniak

et al. 2024

Drugs - Real World Outcomes

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Background and Objective The tyrosine kinase inhibitors cabozantinib and axitinib have been widely used in England to treat advanced renal cell carcinoma following prior vascular endothelial growth factor-targeted therapy, but data on real-world usage remain limited. Our objective was to describe the real-world treatment patterns and outcomes of patients with advanced renal cell carcinoma who received second-line or later-line (≥ 2L) cabozantinib or axitinib after vascular endothelial growth factor-targeted therapy in clinical practice in England. Methods This retrospective cohort study used clinical practice data (collected 2011–20) from the English Cancer Analysis System database. Patient characteristics, treatment sequence and duration, and overall survival (time from initiation of cabozantinib/axitinib treatment to death) were evaluated. Results Data from 1485 eligible adults with advanced renal cell carcinoma were analyzed: 440 received ≥ 2L cabozantinib (2L for 88.6% of them); 1045 received ≥ 2L axitinib (2L for 89.5%). The most common first-line treatments were sunitinib (2L cabozantinib subcohort, 48%; 2L axitinib subcohort, 46%) and pazopanib (46% and 54%, respectively); nivolumab was the most common third-line treatment (18% and 19%, respectively). Median (interquartile range) 2L therapy duration was 5.52 (2.73–11.74) months for cabozantinib and 4.60 (1.45–12.36) months for axitinib. Following adjustment for potential confounders using inverse probability weighting, overall survival (median [interquartile range]) was longer for ≥ 2L cabozantinib (11.2 [5.7–28.0] months) than for ≥ 2L axitinib (10.4 [4.7–22.0] months; log-rank p = 0.0034). Conclusions The Cancer Analysis System database is a valuable research resource providing extensive real-world clinical data. Real-world overall survival was longer with ≥ 2L cabozantinib than with axitinib. Clinical Trial Registration ClinicalTrials.gov, NCT04637204; registered November 2020. Supplementary Information The online version contains supplementary material available at 10.1007/s40801-023-00415-w.

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CABOSEQ: The Effectiveness of Cabozantinib in Patients With Treatment Refractory Advanced Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC)

Cited by 13 publications

References 24 publications

Activity of cabozantinib in further line treatment of metastatic clear cell renal cell carcinoma. Real-world experience in a single-center retrospective study

Activity of cabozantinib in further line treatment of metastatic clear cell renal cell carcinoma. Real-world experience in a single-center retrospective study

Identification of genomic drivers for the therapeutic response of Cabozantinib in patients with metastatic renal cell carcinoma

Cabozantinib and Axitinib After Vascular Endothelial Growth Factor Therapy in Patients with Advanced Renal Cell Carcinoma: A Retrospective Cohort Study from England

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