Efficacy and Prognostic Factors of Sunitinib as First-Line Therapy for Patients With Metastatic Renal Cell Carcinoma in an Arab Population

Badran, Ahmed; Elshenawy, Mahmoud A; Shahin, Ahmed N.; Aljubran, Ali; Alzahrani, Ahmed; Eldali, Abdelmoneim; Bazarbashi, Shouki

doi:10.1200/jgo.19.00111

Cited by 8 publications

(4 citation statements)

References 48 publications

(54 reference statements)

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“…Of note, the lowest reported progressive disease rate in the contemporary studies was 13.7, observed in the CHECKMATE 9ER trial. 12 Additionally, the PFS duration of 16.5 months was more than double that of our historical control 23 and is similar to the PFS rate obtained with the new CPI-containing regimens. Despite this study being a phase I/II trial, the patients’ characteristics clearly represent an unselected group, with only 28% of the patients having an ECOG performance status of zero and only 12% in the favorable IMDC risk group.…”

Section: Discussionsupporting

confidence: 80%

“…The study was later amended to a planned enrollment of 39 patients after the publication of the real-world data of sunitinib in our population, which showed a response rate of 30% and PFS duration of 6 months. 23 This number was based on the single-stage phase II design 24 to test a null hypothesis of H0: P ≤ .3 versus an alternative hypothesis of P ≥ .5 with a significance level of 5% and power of 80%, where P represents the response rate.…”

Section: Methodsmentioning

confidence: 99%

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Combining Sunitinib and Bevacizumab for the Management of Advanced Renal Cell Carcinoma: A Phase I/II Trial

et al. 2023

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Background Tyrosine kinase inhibitors remain a cornerstone in managing metastatic clear cell renal cell carcinoma (RCC). The 4 weeks on/2 weeks off intermittent sunitinib schedule could result in rebound angiogenesis and tumor progression in the 2-week rest period. We propose using bevacizumab during this period for continuous antiangiogenic effects. Method This was a phase I/II study of patients with advanced clear cell RCC. Sunitinib was given 50 mg daily on a 4-week on/2-week off schedule. Bevacizumab was given on day 29 of each sunitinib cycle. The bevacizumab starting dose was 5 mg/kg, and the dose was escalated to 10 mg if there was no dose-limiting toxicity. The primary endpoints were response rate and progression-free survival (PFS). Results Twenty-five patients were recruited. The study was closed prematurely because of poor accrual. No dose-limiting toxicity was observed with 5 mg bevacizumab. One patient achieved a complete response, and 12 achieved a partial response (52% response rate). At a median follow-up of 42.2 months (95%, confidence interval (CI) 32.9 to 51.4), the median PFS duration was 16.5 months (95% CI 4.1-28.8), and the median overall survival time was 33.3 months (95% CI 19.4-47.3). Twenty-two patients (88%) had at least one grade 3 or 4 toxicity; the most common were thrombocytopenia (32%), lymphopenia (32%), hypertension (28%), and fatigue (24%). Conclusion Continuous angiogenesis blockade by adding bevacizumab to the sunitinib on/off regimen for advanced RCC yields significant antitumor activity with manageable increased toxicity.

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Section: Discussionsupporting

confidence: 80%

Section: Methodsmentioning

confidence: 99%

Combining Sunitinib and Bevacizumab for the Management of Advanced Renal Cell Carcinoma: A Phase I/II Trial

et al. 2023

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“…Therefore, a direct comparison of the results with data from the literature is not possible. However, according to the results of one retrospective study, it has been shown that patients who start therapy within the first 100 days from the time of diagnosis have a statistically significant faster progression of the disease (18). In this study, 27% of patients permanently discontinued therapy due to disease progression or death for any reason within 12 months of initiating targeted therapy.…”

Section: Discussionmentioning

confidence: 61%

Association between time from diagnosis to initiation of systemic therapy of metastatic renal cell carcinoma with treatment outcome

Lisičić,

Kević,

Savić

et al. 2023

Medicinski podmladak

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Introduction: In about 30% of cases, renal cell carcinoma (RCC) is detected initially in the metastatic stage (mRCC). The mainstay of mRCC treatment is anti-angiogenesis targeted therapy and immunotherapy which both have significantly prolonged progression-free survival and overall survival in patients with mRCC. Aim: The aim of this study was to examine the association between the time interval from diagnosis of mRCC to the start of systemic therapy with the radiologically assessed best treatment response after 12 months of therapy. Material and methods: This observational study included 85 patients diagnosed initially in the metastatic stage of RCC. All patients received single-agent systemic targeted therapy sunitinib. The minimum follow-up period was 12 months. The radiologic assessment was performed after every 3 months, and the RECIST criteria were used to evaluate the best treatment response. Results: The mean time interval from mRCC diagnosis to the start of systemic targeted therapy was 3.5 ± 2.5 months, with a median of 2 months. No statistically significant association was observed between the best radiologically assessed treatment response after 12 months of therapy and the time interval from diagnosis of mRCC to the start of systemic targeted therapy (p = 0.7). Moreover, no statistically significant association was found between the best radiologically assessed treatment response after 12 months of therapy and a total number of metastatic sites at baseline. Conclusion: No association was observed between the best radiologically assessed treatment response after 12 months of systemic targeted therapy, neither with the time interval from mRCC diagnosis to the start of systemic targeted therapy nor with the total number of metastatic sites in patients who were initially diagnosed with mRCC and received sunitinib in first-line setting.

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“…RCCs are generally divided into five subtypes: clear cell, papillary, chromophobe, collecting duct, and unclassified, among which the first three constitute the majority of RCCs ( Truong and Shen, 2011 ). Although advances in the medical and surgical management of RCCs have been made ( Rini et al, 2009 ; Bazarbashi et al, 2023 ), the outcomes associated with the tumor remain relatively poor ( Badran et al, 2020 ). Additionally, differentiating between different subtypes of RCC is still difficult.…”

Section: Aberrant Expression Of Claudins In Renal Cell Carcinomasmentioning

confidence: 99%

Claudins in genitourinary tract neoplasms: mechanisms, prognosis, and therapeutic prospects

Arabi,

Fawzy,

Sabbah

et al. 2023

Front. Cell Dev. Biol.

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Genitourinary (GU) cancers are among the most prevalent neoplasms in the world, with bladder cancers constituting 3% of global cancer diagnoses. However, several pathogenetic mechanisms remain controversial and unclear. Claudins, for example, have been shown to play a significant role in several cancers of the human body. Their role in GU cancers has not been extensively studied. Aberrant expression of claudins −1, −2, −3, −4, −7, and −11 has been expressed in urothelial cell carcinomas. In prostate cancers, altered levels of claudins −1, −2, −3, −4, and −5 have been reported. Furthermore, the levels of claudins −1, −2, −3, −4, −6, −7, −8, and −10 have been studied in renal cell carcinomas. Specifically, claudins −7 and −8 have proven especially useful in differentiating between chromophobe renal cell carcinomas and oncocytomas. Several of these claudins also correlate with clinicopathologic parameters and prognosis in GU cancers. Although mechanisms underpinning aberrant expression of claudins in GU cancers are unclear, epigenetic changes, tumor necrosis factor-ɑ, and the p63 protein have been implicated. Claudins also provide therapeutic value through tailored immunotherapy via molecular subtyping and providing therapeutic targets, which have shown positive outcomes in preclinical studies. In this review, we aim to summarize the literature describing aberrant expression of claudins in urothelial, prostatic, and renal cell carcinomas. Then, we describe the mechanisms underlying these changes and the therapeutic value of claudins. Understanding the scope of claudins in GU cancers paves the way for several diagnostic, prognostic, and therapeutic innovations.

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Efficacy and Prognostic Factors of Sunitinib as First-Line Therapy for Patients With Metastatic Renal Cell Carcinoma in an Arab Population

Cited by 8 publications

References 48 publications

Combining Sunitinib and Bevacizumab for the Management of Advanced Renal Cell Carcinoma: A Phase I/II Trial

Combining Sunitinib and Bevacizumab for the Management of Advanced Renal Cell Carcinoma: A Phase I/II Trial

Association between time from diagnosis to initiation of systemic therapy of metastatic renal cell carcinoma with treatment outcome

Claudins in genitourinary tract neoplasms: mechanisms, prognosis, and therapeutic prospects

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