Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors

Santoni, Matteo; Heng, Daniel Yick Chin; Bracarda, Sergio; Procopio, Giuseppe; Milella, Michèle; Porta, Camillo; Matrana, Marc; Cartenì, Giacomo; Crabb, Simon J.; Giorgi, Ugo De; Basso, Umberto; Masini, Cristina; Calabrò, Fabio; Vitale, Maria Giuseppa; Santini, Daniele; Massari, Francesco; Galli, Luca; Fornarini, Giuseppe; Ricotta, Riccardo; Buti, Sebastiano; Zucali, Paolo Andrea; Caffo, Orazio; Morelli, Franco; Carrozza, Francesco; Martignetti, Angelo; Iacovelli, Roberto; Mosca, Alessandra; Atzori, Francesco; Vau, Nuno; Incorvaia, Lorena; Ortega, Cinzia; Scarpelli, Marina; López-Beltrán, Antonio; Cheng, Liang; Paolucci, V.; Graham, Jeffrey; Pierce, Erin; Scagliarini, Sarah; Sepe, Pierangela; Verzoni, Elena; Merler, Sara; Rizzo, Mimma; Sorgentoni, Giulia; Conti, Alessandro; Piva, Francesco; Cimadamore, Alessia; Montironi, Rodolfo; Battelli, Nicola

doi:10.3390/cancers12010084

Cited by 27 publications

(17 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…VHL gene malfunction is detected in the overwhelming majority of the cases, resulting in a pseudo-hypoxic status that promotes angiogenesis [ 5 ]. The implementation of antiangiogenic therapies with tyrosine kinase inhibitors has improved the prognosis of many of these patients [ 6 , 7 ]. However, its efficacy is limited due to the development of resistant-to-therapy cell clones [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

Larrinaga

Solano-Iturri

Errarte

et al. 2021

Cancers

View full text Add to dashboard Cite

(1). Background: Immunohistochemical (IHC) evaluation of programmed death-1 (PD-1) and its ligand (PD-L1) is being used to evaluate advanced malignancies with potential response to immune checkpoint inhibitors. We evaluated both plasma and tissue expression of PD-1 and PD-L1 in the same cohort of patients, including non-metastatic and metastatic clear cell renal cell carcinoma (CCRCC). Concomitant plasma and tissue expression of PD-1 and PD-L1 was evaluated with emphasis on diagnostic and prognostic implications. (2) Methods: we analyzed PD-1 and PD-L1 IHC expression in tumor tissues and soluble forms (sPD-1 and sPD-L1) in plasma from 89 patients with CCRCC, of which 23 were metastatic and 16 received systemic therapy. The primary endpoint was evaluation of overall survival using Kaplan-Meier analysis and the Cox regression model. Plasma samples from healthy volunteers were also evaluated. (3) Results: Interestingly, sPD-1 and sPD-L1 levels were lower in cancer patients than in controls. sPD-1 and sPD-L1 levels and their counterpart tissue expression both at the tumor center and infiltrating front were not associated. Higher expression of both PD-1 and PD-L1 were associated with tumor grade, necrosis and tumor size. PD-1 was associated to tumor stage (pT) and PD-L1 to metastases. sPD-1 and sPD-L1 were not associated with clinico-pathological parameters, although both were higher in patients with synchronous metastases compared to metachronous ones and sPD-L1 was also higher for metastatic patients compared to non-metastatic patients. sPD-1 was also associated with the International Metastatic Renal Cell Cancer Database Consortium (IMDC) prognostic groups in metastatic CCRCC and also to the Morphology, Attenuation, Size and Structure (MASS) response criteria in metastatic patients treated with systemic therapy, mainly tyrosine-kinase inhibitors. Regarding prognosis, PD-L1 immunostaining at the tumor center with and without the tumor front was associated with worse survival, and so was sPD-L1 at a cut-off >793 ng/mL. Combination of positivity at both the tissue and plasma level increased the level of significance to predict prognosis. (4) Conclusions: Our findings corroborate the role of PD-L1 IHC to evaluate prognosis in CCRCC and present novel data on the usefulness of plasma sPD-L1 as a promising biomarker of survival in this neoplasia.

show abstract

Section: Introductionmentioning

confidence: 99%

Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

Larrinaga

Solano-Iturri

Errarte

et al. 2021

Cancers

View full text Add to dashboard Cite

show abstract

“…Currently, cabozantinib is approved for the treatment of patients with metastatic RCC in treatment-naïve adults with intermediate or poor-risk features and for adults that have progressed to prior vascular endothelial growth factor/receptor inhibitors. In 2019, we reported the results of an international retrospective real-world analysis on cabozantinib in previously treated patients with metastatic RCC, which was aimed at investigating the presence of prognostic factors in this context [ 10 ]. We observed that both hemoglobin (Hb) levels and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic models were associated with the outcome of patients receiving cabozantinib [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…In 2019, we reported the results of an international retrospective real-world analysis on cabozantinib in previously treated patients with metastatic RCC, which was aimed at investigating the presence of prognostic factors in this context [ 10 ]. We observed that both hemoglobin (Hb) levels and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic models were associated with the outcome of patients receiving cabozantinib [ 10 ]. Furthermore, the median time to strategy failure (TTSF) was 11.57 months with the sequence cabozantinib–nivolumab and 25.64 months with nivolumab–cabozantinib [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

“…We observed that both hemoglobin (Hb) levels and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic models were associated with the outcome of patients receiving cabozantinib [ 10 ]. Furthermore, the median time to strategy failure (TTSF) was 11.57 months with the sequence cabozantinib–nivolumab and 25.64 months with nivolumab–cabozantinib [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?

et al. 2021

Self Cite

View full text Add to dashboard Cite

We analyzed the clinical and pathological features of renal cell carcinoma (RCC) patients treated with cabozantinib stratified by body mass index (BMI). We retrospectively collected data from 16 worldwide centers involved in the treatment of RCC. Overall survival (OS) and progression-free survival (PFS) were analyzed using Kaplan–Meier curves. Cox proportional models were used at univariate and multivariate analyses. We collected data from 224 patients with advanced RCC receiving cabozantinib as second- (113, 5%) or third-line (111, 5%) therapy. The median PFS was significantly higher in patients with BMI ≥ 25 (9.9 vs. 7.6 months, p < 0.001). The median OS was higher in the BMI ≥ 25 subgroup (30.7 vs. 11.0 months, p = 0.003). As third-line therapy, both median PFS (9.2 months vs. 3.9 months, p = 0.029) and OS (39.4 months vs. 11.5 months, p = 0.039) were longer in patients with BMI ≥ 25. BMI was a significant predictor for both PFS and OS at multivariate analysis. We showed that a BMI ≥ 25 correlates with longer survival in patients receiving cabozantinib. BMI can be easily assessed and should be included in current prognostic criteria for advanced RCC.

show abstract

“…We observed activity of cabozantinib in patients who had previously received ICI, with a DCR of 64% and median OS of 15.8 months (range 10.3 -20.7 months). Similar findings were seen in the METEOR study as well as other retrospective series [16][17][18][19][20]. Importantly, we included patients treated immediately after first-line ICI-based combination therapy (Table 3), which represents a group where data is lacking on the optimal treatment strategy.…”

Section: Discussionmentioning

confidence: 86%

Real-Word Experience of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC): Results from the Canadian Kidney Cancer information system (CKCis)

Zhang

Basappa

Ghosh

et al. 2021

KCA

Self Cite

View full text Add to dashboard Cite

Background: Cabozantinib is an oral multitargeted tyrosine kinase inhibitor (TKI) that has demonstrated efficacy in metastatic renal-cell carcinoma (mRCC) randomized trials. Objective: To explore the real-world effectiveness of cabozantinib in pretreated patients with mRCC, including patients who progressed on immune-oncology checkpoint inhibitor (ICI) therapy. Methods: Using the Canadian Kidney Cancer information system (CKCis), patients with mRCC treated with cabozantinib monotherapy as second-line or later from January 1, 2011 to September 1, 2019 were identified. Patients were stratified based on line of cabozantinib received. We reported overall survival (OS), time to treatment failure (TTF) and disease control rate (DCR). Prognostic variables were analyzed using multivariable analysis. Results: 157 patients received cabozantinib (median TTF 8.0 months; median OS 15.8 months): 37 (24%) in the second line (median TTF 10.4 months; median OS 18.9 months) 66 (42%) in third line (median TTF 5.9 months; median OS 13.3 months) and 54 (34%) in either 4th or 5th line (median TTF 9.4 months; median OS 16.8 months). One hundred sixteen patients (74%) received cabozantinib after prior ICI therapy (median TTF of 7.6 months; median OS of 15.8 months). DCR in all patients was 63% with 46%, 65% and 72% in 2nd line, 3rd line and 4th/5th line patients respectively. DCR in patients who received cabozantinib after prior ICI therapy was 64%. Conclusions: Cabozantinib is effective in a real-world, unselected population of mRCC patients, including in those who have progressed on prior ICI therapy, and in those exposed to multiple lines of therapy.

show abstract

Real-World Data on Cabozantinib in Previously Treated Patients with Metastatic Renal Cell Carcinoma: Focus on Sequences and Prognostic Factors

Cited by 27 publications

References 22 publications

Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

Soluble PD-L1 Is an Independent Prognostic Factor in Clear Cell Renal Cell Carcinoma

Body Mass Index in Patients Treated with Cabozantinib for Advanced Renal Cell Carcinoma: A New Prognostic Factor?

Real-Word Experience of Cabozantinib in Metastatic Renal Cell Carcinoma (mRCC): Results from the Canadian Kidney Cancer information system (CKCis)

Contact Info

Product

Resources

About