Clinical Activity of Sunitinib Rechallenge in Metastatic Renal Cell Carcinoma (Mrcc) – Results of the Resume Study

Оудард, С.; Goupil, Marine Gross; Geoffrois, L.; Guillot, Aline; Chevreau, Christine; Deville, Jean‐Laurent; Falkowski, Sławomir; Boyle, H.; Palmaro, M. Baciuchka; Gimel, P.; Laguerre, Brigitte; Laramas, Mathieu; Pfister, C.; Topard, D.; Rolland, Frédéric; Legouffe, Eric; Amela, Eric Yaovi; Abadie‐Lacourtoisie, Sophie; Mahi, Naim Al

doi:10.1093/annonc/mdu337.9

Cited by 6 publications

(3 citation statements)

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“…Previous results obtained from experiments in mice had already suggested that RCC tumours could still re-gain sensitivity to sunitinib or sorafenib after failed response or resistance to the same drugs [37,38]. In this sense, re-introduction of sunitinib as second-, third-or subsequent lines of therapy after RCC progression has proven efficacy [39][40][41][42][43]. All these results suggested that changes in the tumour microenvironment or temporal breaks between treatments could favour the re-gain of tumour sensitivity to targeted therapy.…”

Section: Discussionmentioning

confidence: 98%

Outcomes of systemic targeted therapy in recurrent renal cell carcinoma treated with adjuvant sunitinib

et al. 2021

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To assess the efficacy and tolerability of rechallenge with sunitinib and other targeted therapies (TTs) in patitents with relapsed recurrent renal cell carcinoma (RCC) in the advanced setting. MethodsIn this multi-institutional retrospective study, patients with relapsed RCC were rechallenged with sunitinib or other systemic TTs as a first-line therapeutic approach after failed adjuvant sunitinib treatment. Patient characteristics, treatments and clinical outcomes were recorded. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR) and overall survival (OS). ResultsA total of 34 patients with relapses were recorded, and 25 of these (73.5%) were men. Twenty-five patients were treated with systemic TT: 65% of patients received TT against the vascular endothelial growth factor pathway (including sunitinib), 21.7% received mammalian target of rapamycin inhibitors and 13% received immunotherapy. The median (interquartile range) time to relapse was 20.3 (5.2-20.4) months from diagnosis, and 7.5 months (1.0-8.5) from the end of adjuvant suntinib treatment. At a median follow-up of 23.5 months, 24 of the 25 patients had progressed on first-line systemic therapy. The median PFS was 12.0 months (95% confidence interval [CI] 5.78-18.2). There were no statistical differences in PFS between different treatments or sunitinib rechallenge. PFS was not statistically different in patients relapsing on or after adjuvant suntinib treatment (≤ 6 or >6 months after adjuvant suntinib ending). The ORR was 20.5%. The median OS was 29.1 months (95% CI 16.4-41.8). ConclusionsRechallenge with sunitinib or other systemic therapies is still a feasible therapeutic option that provides patients with advanced or metastastic RCC with additional clinical benefits with regard to PFS and OS after failed response to adjuvant sunitinib.

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Section: Discussionmentioning

confidence: 98%

Outcomes of systemic targeted therapy in recurrent renal cell carcinoma treated with adjuvant sunitinib

et al. 2021

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“…These methodological problems could have led to variations in dose adjustment, treatment schedule, and radiographic assessment, which may have subsequently influenced PFS. Table 3 shows the results of several of these trials (24,(119)(120)(121)(122)(123).…”

Section: Clinical Evidence Regarding the Use Of Targeted Therapies Afmentioning

confidence: 99%

“…In contrast to studies that used a different TKI from that used as the first-line treatment, the RESUME study evaluated the clinical activity of sunitinib rechallenge in patients with mRCC (123). All patients received first-line sunitinib, then one or more other treatments (temsirolimus, everolimus, sorafenib, pazopanib, axitinib and bevacizumab), followed by sunitinib rechallenge.…”

Section: Clinical Evidence Regarding the Use Of Targeted Therapies Afmentioning

confidence: 99%

Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action

Durán¹,

Lambea²,

Maroto³

et al. 2016

Targ Oncol

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Renal cell carcinoma (RCC) is a complex disease characterized by mutations in several genes. Loss of function of the von Hippel-Lindau (VHL) tumour suppressor gene is a very common finding in RCC and leads to up-regulation of hypoxia-inducible factor (HIF)-responsive genes accountable for angiogenesis and cell growth, such as platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Binding of these proteins to their cognate tyrosine kinase receptors on endothelial cells promotes angiogenesis. Promotion of angiogenesis is in part due to the activation of the phosphatidylinositol-3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathway. Inhibition of this pathway decreases protein translation and inhibits both angiogenesis and tumour cell proliferation. Although tyrosine kinase inhibitors (TKIs) stand as the main first-line treatment option for advanced RCC, eventually all patients will become resistant to TKIs. Resistance can be overcome by using second-line treatments with different mechanisms of action, such as inhibitors of mTOR, c-MET, programmed death 1 (PD-1) receptor, or the combination of an mTOR inhibitor (mTORi) with a TKI. In this article, we briefly review current evidence regarding mechanisms of resistance in RCC and treatment strategies to overcome resistance with a special focus on the PI3K/AKT/mTOR pathway.

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Efficacy of Rechallenge of Metastatic Renal Cell Carcinoma Patient With Sunitinib After Prior Resistance to Axitinib: Case Report and Review of the Literature

Daste

Gross‐Goupil

Quivy

et al. 2016

Clinical Genitourinary Cancer

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Clinical Activity of Sunitinib Rechallenge in Metastatic Renal Cell Carcinoma (Mrcc) – Results of the Resume Study

Cited by 6 publications

References 0 publications

Outcomes of systemic targeted therapy in recurrent renal cell carcinoma treated with adjuvant sunitinib

Outcomes of systemic targeted therapy in recurrent renal cell carcinoma treated with adjuvant sunitinib

Resistance to Targeted Therapies in Renal Cancer: The Importance of Changing the Mechanism of Action

Efficacy of Rechallenge of Metastatic Renal Cell Carcinoma Patient With Sunitinib After Prior Resistance to Axitinib: Case Report and Review of the Literature

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