VEGFR TKI ‘resistance’ or transient clinical insensitivity to VEGFR TKI in metastatic renal cell carcinoma

Ravaud, Alain; Digue, Laurence; Trufflandier, Nathalie; Smith, Denis

doi:10.1093/annonc/mdp548

Cited by 18 publications

(8 citation statements)

References 5 publications

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“…The present study is the final evaluation of our previously presented preliminary data [ 7 ] investigating sunitinib rechallenge in patients with mRCC. As well as retrospective investigations [ 8 – 11 ] and case reports [ 12 – 14 ], the preliminary result of a recent prospective study was also presented [ 15 ] (Table 3 ). In another study, it was stated that re-exposure to TKI after previous sunitinib and subsequent everolimus treatment may have clinical benefit, but unfortunately the sunitinib rechallenge was not explicitly reported [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Sunitinib Rechallenge After Other Targeted Therapies in Metastatic Renal Cell Carcinoma Patients: A Single-Center, Retrospective Study

et al. 2019

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Background Sunitinib is still one of the standard therapies in metastatic renal cell carcinoma (mRCC). Despite the benefit of sunitinib resistance will develop in the majority of patients. Most of them receive multiple sequential therapies during the course of disease. Objectives To retrospectively investigate the efficacy and safety of rechallenged sunitinib in third or later line settings. Patients and Methods Twenty-one mRCC patients were identified who received rechallenged sunitinib between March 2010 and April 2018. Patients received sunitinib in first or second line, then other tyrosine kinase and/or mTOR inhibitors were applied, then sunitinib was rechallenged. Patients’ characteristics, tolerability, treatment modalities, and treatment outcomes were recorded. The primary end-point was progression-free survival (PFS) of rechallenged sunitinib. Results Median age of patients was 62 years at the start of sunitinib rechallenge. Sixty-seven percent of patients were male. All patients had prior nephrectomy. Upon rechallenge 4 patients achieved partial response and 12 stable disease. The median PFS of first sunitinib treatment was 22 (95% CI 17–26) months and for rechallenged sunitinib 14 (95% CI 6–20) months. No increased severity of prior toxicity or new adverse events was reported during rechallenged sunitinib. The median overall survival (OS) from the start of first sunitinib was 67 (95% CI 46–76) months. Multivariate Cox regression analysis revealed that younger age (< 57 years) at start of first sunitinib (HR = 0.24; 95% CI 0.07–0.79; p = 0.019) and longer (> 2 years) first sunitinib treatment (HR = 0.28; 95% CI 0.09–0.93; p = 0.038) were independent markers of longer OS. Conclusion Sunitinib rechallenge is a feasible and tolerable option with clinical benefit in selected mRCC patients.

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Section: Discussionmentioning

confidence: 99%

Sunitinib Rechallenge After Other Targeted Therapies in Metastatic Renal Cell Carcinoma Patients: A Single-Center, Retrospective Study

et al. 2019

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“…However, acquired resistance in ccRCC may result a reversible event [63]: as demonstrated in several studies, the protracted exposure of tumor cells to sunitinib constantly results in drug resistance development in vitro [65,66]. Gotink et al in 2011 verified that sensitivity to sunitinib may be progressively restored after a 12-week period of drug-free culture [67].…”

Section: Resistancementioning

confidence: 99%

Recent Aspects of Sunitinib Therapy in Patients with Metastatic Clear-Cell Renal Cell Carcinoma: a Systematic Review of the Literature

et al. 2015

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Sunitinib is an orally available inhibitor of multiple tyrosine-kinase receptors approved for the treatment of advanced clear-cell renal cell carcinoma (ccRCC), a disease which has habitually had a very poor patient survival rate. Although it has become the most widely used drug for this disease, it remains not completely clear the best treatment strategy with these agent. The aim of this review is to highlight the most recent and interesting aspects of the research on treatment of advanced ccRCC with sunitinib and eventually determine alternative treatment schedule to reduce the incidence of side effects; we also wanted to review recent biomarkers able to predict response to therapy and also to point out the mechanism of acquired resistance to this drug.

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“…The situation is quite different in third line, as the question of re-challenging with a VEGF-R TKI is raised. In a case report in 2009, our group showed that a VEGF-R TKI 'resistance' could be outmatched by a re-challenge in third line [76]. This has been confirmed by a larger cohort, with 15 patients retrospectively analysed, to whom sunitinib was re-introduced in third line with nine objective responses [77].…”

Section: Choices Between Treatment and Sequence Of Treatmentmentioning

confidence: 69%

Protein kinase inhibitors in renal cell carcinoma

Daste

Grellety

Gross‐Goupil

et al. 2013

Expert Opinion on Pharmacotherapy

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VEGF TKI and m-TOR inhibitors have significantly improved the outcome of mRCC and offer a gain in survival by sequential treatments for the majority of patients. But they induce a particular toxicity profile. An adequate management of each drug and its sequence in treatment is essential to optimise the outcome and preserve the quality of life (QoL) of patients with mRCC. In forthcoming years, pending results should indicate whether VEGF TKI are of interest in an adjuvant setting and if new drugs targeting will challenge the current standard guidelines in the metastatic setting.

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VEGFR TKI ‘resistance’ or transient clinical insensitivity to VEGFR TKI in metastatic renal cell carcinoma

Cited by 18 publications

References 5 publications

Sunitinib Rechallenge After Other Targeted Therapies in Metastatic Renal Cell Carcinoma Patients: A Single-Center, Retrospective Study

Sunitinib Rechallenge After Other Targeted Therapies in Metastatic Renal Cell Carcinoma Patients: A Single-Center, Retrospective Study

Recent Aspects of Sunitinib Therapy in Patients with Metastatic Clear-Cell Renal Cell Carcinoma: a Systematic Review of the Literature

Protein kinase inhibitors in renal cell carcinoma

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