Activity of Systemic Treatments After Cabozantinib Failure in Advanced Metastatic Renal Cell Carcinoma

Cerbone, Luigi; Nunno, Vincenzo Di; Ajuria, L. Carril; Silva, Carolina Alves Costa; Colomba, Emeline; Guida, Annalisa; Salviat, Flore; Hirsch, Laure; Benchimol-Zouari, A.; Flippot, Ronan; Escudier, Bernard; Albigès, Laurence

doi:10.1016/j.clgc.2021.09.001

Cited by 8 publications

(6 citation statements)

References 25 publications

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“…These authors found an OS of 7.7 months and an ORR of 8.7%, achieving PR in two patients on axitinib and two on ICIs. 29 In agreement with previous reports, our findings show that everolimus is the most common 4 L and beyond treatment, followed by sorafenib. 26 Everolimus was investigated in the phase III double-blind, randomized, placebo-controlled RECORD-1 in patients who progressed under treatment with one or two TKIs, leading to improved PFS (4.0 months vs. 1.9 months; HR, 0.33; p < 0.001).…”

Section: Discussionsupporting

confidence: 93%

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Effect of systemic therapies or best supportive care after disease progression to both nivolumab and cabozantinib in metastatic renal cell carcinoma: The Meet‐Uro 19BEYOND study

et al. 2022

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Section: Discussionsupporting

confidence: 93%

“…Recently, Cerbone et al conducted a retrospective study on heavily pre‐treated mRCC patients undergoing systemic therapy after cabozantinib failure. These authors found an OS of 7.7 months and an ORR of 8.7%, achieving PR in two patients on axitinib and two on ICIs 29 …”

Section: Discussionmentioning

confidence: 93%

Effect of systemic therapies or best supportive care after disease progression to both nivolumab and cabozantinib in metastatic renal cell carcinoma: The Meet‐Uro 19BEYOND study

et al. 2022

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“…For patients who progress on salvage cabozantinib, therapeutic options include lenvatinib/everolimus [17], but are otherwise limited. After progression on cabozantinib, there is limited benefit from other TKIs [18].…”

Section: Introductionmentioning

confidence: 99%

Extended Disease Control with Unconventional Cabozantinib Dose Increase in Metastatic Renal Cell Carcinoma1

Sharma

Elias

Christie

et al. 2022

KCA

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BACKGROUND: Cabozantinib is among the most potent tyrosine kinase inhibitors (TKIs) FDA-approved for metastatic renal cell carcinoma (mRCC). Effective treatments after progression on cabozantinib salvage therapy are limited. Dose escalation for other TKIs has been shown to afford added disease control. OBJECTIVE: We sought to evaluate whether dose escalation of cabozantinib (Cabometyx®) from conventional doses in selected patients with limited treatment options offered additional disease control. We asked how cabozantinib dose increases may affect circulating drug levels. METHODS: We identified patients with mRCC at the University of Texas Southwestern Medical Center who were treated with cabozantinib dose escalation to 80 mg after progressing on conventional cabozantinib 60 mg. We then queried leading kidney cancer investigators across the world to identify additional patients. Finally, we reviewed pharmacokinetic (PK) data to assess how higher doses impacted circulating levels by comparison to other formulations (Cometriq® capsules). RESULTS: We report six patients treated at two different institutions with cabozantinib-responsive disease and good tolerability, where cabozantinib was dose escalated (typically to 80mg, but as high as 120 mg) after progression on 60 mg, a strategy that resulted in added disease control (median duration, 14 months; 95% Confidence Interval [CI]: 8 –Not Estimable[NE]). Four patients (66.7%) had disease control lasting at least 1 year. No grade III/IV adverse events were identified. A comparison of PK data to FDA-approved cabozantinib 140 mg capsules suggest that cabozantinib 80 mg tablets results in comparable exposures. CONCLUSIONS: mRCC patients with cabozantinib responsive disease and reasonable tolerability may benefit from dose escalation at progression.

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“…Based on this assurance, the description of HPD is mainly dependent on several parameters: TGR, TGK, and TTF. Definitions of these terms are mentioned in “methods.” TTF refers to the duration between the beginning of immunotherapy to drug discontinuation for any reason, including toxicity, disease progression, and even death ( 64 ). The TGR-dependent definition of HPD in eligible studies included “TGR post /TGR pre ≥ 2” or “TGR post /TGR pre ≥ 4,” whereas certain studies define HPD as “(TGR post - TGR pre) /TGR pre ≥ 50%” or “> 40% increase in ΔTGR.” For the TGK-dependent definition of HPD, popular criteria were “TGK post /TGK pre ≥ 2” or “TGK post /TGK pre ≥ 4.” Whatever the usage of TGR or TGK, most studies add the TTF ≤ 2 because rapid progression is an essential trait of HPD.…”

Section: Resultsmentioning

confidence: 99%

“…Definitions of these terms are mentioned in "methods." TTF refers to the duration between the beginning of immunotherapy to drug discontinuation for any reason, including toxicity, disease progression, and even death (64). The TGR-dependent definition of HPD in eligible studies included "TGR post /TGR pre ≥ 2" or "TGR post /TGR pre ≥ 4," whereas certain studies define HPD as "(TGR post -TGR pre) / TGR pre ≥ 50%" or "> 40% increase in DTGR."…”

Section: Resultsmentioning

confidence: 99%

Hyperprogressive disease in patients suffering from solid malignancies treated by immune checkpoint inhibitors: A systematic review and meta-analysis

et al. 2022

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IntroductionHyperprogressive disease (HPD) is a paradoxically rapid disease progression during or shortly after antitumor treatment, especially immune checkpoint inhibitors (ICIs). Various diagnosis criteria of HPD cause heterogeneous incidence rates in different clinical research, and there is no consensus on potential risk factors associated with HPD occurrence. Hence, we aimed to summarize incidence of HPD in ICI treatment for solid tumors. Clinicopathological factors associated with HPD are also analyzed.MethodsClinical studies about HPD during/after ICI treatment of solid malignancies are included. Pubmed, Embase, and Cochrane library were searched for eligible studies published before October 7. The Newcastle–Ottawa scale was used to assess the quality of the included studies. Random effect and fixed effect models were, respectively, used for pooling incidence of HPD and analysis of risk factors for HPD. Heterogeneity, subgroup analysis, and publication bias were also analyzed. All meta-analysis was performed via R software (y -40v4.0.2).ResultsForty-one studies with 6009 patients were included. The pooled incidence of HPD was 13.2% (95% CI, 11.2%–15.4%). Head and neck cancer (HNC) had the highest incidence of HPD (18.06%), and melanoma had the lowest (9.9%). Tumor types (P = .0248) and gender ratio (P = .0116) are sources of heterogeneity of pooled incidence of HPD. For five clinicopathological factors associated with HPD, only programmed cell death protein 1 ligand 1 (PD-L1) positivity was a preventive factor (odds ratio = 0.61, P <.05). High lactate dehydrogenase (LDH) level (OR = 1.51, P = .01), metastatic sites >2 (OR = 2.38, P <.0001), Eastern Cooperative Oncology Group Performance Score ≥2 (OR = 1.47, P = .02), and liver metastasis (OR = 3.06, P <.0001) indicate higher risk of HPD.ConclusionsThe pooled incidence of HPD was less than 15%, and HNC had the highest incidence of HPD. LDH and PD-L1 are remarkable biomarkers for prediction of HPD in future medical practice.

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Activity of Systemic Treatments After Cabozantinib Failure in Advanced Metastatic Renal Cell Carcinoma

Cited by 8 publications

References 25 publications

Effect of systemic therapies or best supportive care after disease progression to both nivolumab and cabozantinib in metastatic renal cell carcinoma: The Meet‐Uro 19BEYOND study

Effect of systemic therapies or best supportive care after disease progression to both nivolumab and cabozantinib in metastatic renal cell carcinoma: The Meet‐Uro 19BEYOND study

Extended Disease Control with Unconventional Cabozantinib Dose Increase in Metastatic Renal Cell Carcinoma1

Hyperprogressive disease in patients suffering from solid malignancies treated by immune checkpoint inhibitors: A systematic review and meta-analysis

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