The efficacy and safety of sunitinib given on an individualised schedule as first-line therapy for metastatic renal cell carcinoma: A phase 2 clinical trial

Bjarnason, Georg A.; Knox, Jennifer J.; Kollmannsberger, Christian; Soulières, Denis; Ernst, D. Scott; Zalewski, Paweł; Canil, Christina; Winquist, Eric; Hotte, Sébastien J.; North, Scott; Heng, Daniel Yick Chin; Macfarlane, Robyn Jane; Venner, Peter; Kapoor, Anil; Hansen, Aaron R.; Eigl, Bernhard J.; Czaykowski, Piotr; Boyd, B.; Wang, Lisa; Basappa, Naveen S.

doi:10.1016/j.ejca.2018.12.006

Cited by 26 publications

(38 citation statements)

References 26 publications

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“…VEGFR-TKI PK parameters can decline over time in spite of constant dosing as has been described for both sorafenib [15,16] and pazopanib [17,18]. A similar decline in sunitinib PK was found in 17/22 patient in the study on individualized sunitinib [2]. This may explain why some patient experience some reduction in side effects as they stay on a constant dose of VEGFR-TKIs long-term and may be an argument for continuous dose/schedule changes to optimize drug exposure.…”

Section: Sunitinibsupporting

confidence: 56%

“…A prospective phase-II study of individualized sunitinib dose and schedule was recently published [2]. Based on the data presented above, it was hypothesized that toxicity-driven dose and schedule changes would optimize drug exposure and improve outcome for each patient.…”

Section: Individualized Sunitinib Studymentioning

confidence: 99%

“…: +1416 480 5847; Fax: +1416 480 6002; E-mail: georg.bjarnason@sunnybrook.ca. been recently published [2]. Some of the general concepts that may also apply to other VEGFR-TKIs are discussed in this section.…”

Section: Introductionmentioning

confidence: 99%

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Individualization of Dose and Schedule Based On Toxicity for Oral VEGF Drugs in Kidney Cancer

Parmar

Bjarnason

2019

Kidney Cancer

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The introduction of oral vascular endothelial growth factor receptor tyrosine kinase inhibitors therapy has been associated with major improvements in outcome for patients with metastatic kidney cancer. Each drug has been licensed with rigid dosing criteria that are not optimal for all patients. This paper reviews the growing body of evidence suggesting that individualized dosing based on toxicity may be associated with optimal drug exposure for each patient and improved outcome both in the metastatic and adjuvant setting.

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Section: Sunitinibsupporting

confidence: 56%

Section: Individualized Sunitinib Studymentioning

confidence: 99%

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Individualization of Dose and Schedule Based On Toxicity for Oral VEGF Drugs in Kidney Cancer

Parmar

Bjarnason

2019

Kidney Cancer

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“…Some studies have reported a higher incidence of AEs in patients receiving sunitinib when compared to the incidence of AEs in patients receiving both pazopanib and sunitinib, which are also first choices of treatment for mRCC [32,33]. In addition, several studies have reported that dose-adjustment according to the individual is effective [34][35][36]. Although the 2/1 schedule may be a way to maintain more drugs because of fewer AEs compared to the 4/2 schedule, it is important to adjust the concentration of the drug appropriately according to the condition of the patient rather than a uniform schedule.…”

Section: Discussionmentioning

confidence: 99%

Does an Alternative Sunitinib Dosing Schedule Really Improve Survival Outcomes Over a Conventional Dosing Schedule in Patients with Metastatic Renal Cell Carcinoma? An Updated Systematic Review and Meta-Analysis

Chung

Kang

Kim

et al. 2019

Cancers

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Treatment-related adverse events (AEs) can obfuscate the maintenance of a conventional schedule of sunitinib in patients with metastatic renal cell carcinoma. Accordingly, alternative schedules seeking to improve the safety profile of sunitinib have been tested. Recently, two meta-analyses similarly described improved safety profiles favoring a two weeks on and one week off (2/1) schedule, but with conflicting results for survival outcomes. Therefore, we conducted an updated systematic review and meta-analysis, including all recently published studies and using complementary statistical methods. Endpoints included progression-free survival, overall survival, and AEs of 15 types. Eleven articles were included in this meta-analysis. Using adjusted findings, we noted statistically better results in progression-free survival (hazard ratio, 0.58; 95% confidence interval, 0.39-0.84; p = 0.005), but no difference in overall survival (hazard ratio, 0.66; 95% confidence interval, 0.42-1.04; p = 0.08). Moreover, the 2/1 schedule was beneficial for reducing the incidence of several AEs. Conclusively, our meta-analysis suggests that the 2/1 schedule holds promise as an alternative means of reducing AEs and maintaining patient quality of life. While the survival outcomes of the 2/1 schedule seem also to be favorable, the level of evidence for this was low, and the interpretation of these findings should warrant caution. Large scale randomized trials are needed to support these results.

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“…For example, dose optimization of sunitinib therapy according to toxicities has been associated with prolonged OS compared to dosing using four weeks on and two weeks off . The longest reported OS was 38.5 months by Bjarnason et al (95% CI 28.3 to not reached) using individualized schedules …”

Section: First Line Systemic Treatment Selectionmentioning

confidence: 99%

Treatment selection for first‐line metastatic renal cell carcinoma in Australia: Impact of new therapy options

Schmidt

Azad

Goh

et al. 2019

Asia-Pac J Clncl Oncology

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Vascular endothelial growth factor receptor tyrosine kinase inhibitors have provided an effective standard of care for the treatment of metastatic clear cell renal cell carcinoma (mRCC). Survival is prolonged with emergence of modern immuno-oncology combination regimens. Prognostic risk assessment is essential for choosing between these therapies to determine the most appropriate first line treatment option, with selection based on International Metastatic RCC Database Consortium Risk Category. We review the current subsidized first line treatments for mRCC in Australia and consider the evidence for treatment selection and sequencing.

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The efficacy and safety of sunitinib given on an individualised schedule as first-line therapy for metastatic renal cell carcinoma: A phase 2 clinical trial

Cited by 26 publications

References 26 publications

Individualization of Dose and Schedule Based On Toxicity for Oral VEGF Drugs in Kidney Cancer

Individualization of Dose and Schedule Based On Toxicity for Oral VEGF Drugs in Kidney Cancer

Does an Alternative Sunitinib Dosing Schedule Really Improve Survival Outcomes Over a Conventional Dosing Schedule in Patients with Metastatic Renal Cell Carcinoma? An Updated Systematic Review and Meta-Analysis

Treatment selection for first‐line metastatic renal cell carcinoma in Australia: Impact of new therapy options

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