Maximising the duration of disease control in metastatic renal cell carcinoma with targeted agents: an expert agreement

The management of metastatic renal cell carcinoma (mRCC) has evolved considerably in the last decade. A number of different systemic molecular targeted agents that have been recently approved have improved the survival of patients with mRCC. This mini-review focuses on the implementation of multi-modality therapy in the management of mRCC and the approved indications of the various available novel agents. These novel agents have expanded our armamentarium and improved clinical outcomes of this challenging disease that has considerable biological heterogeneity and clinical variability.

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Dose escalation of axitinib on disease progression as a strategy in the treatment of metastatic renal cell carcinoma

ESMO Open ◽

10.1136/esmoopen-2018-000445 ◽

2018 ◽

Vol 3 (7) ◽

pp. e000445 ◽

Cited By ~ 2

Author(s):

Gary Joseph Doherty ◽

Deirdre Lynskey ◽

Athena Matakidou ◽

Kate Fife ◽

Tim Eisen

Keyword(s):

Renal Cell Carcinoma ◽

Disease Control ◽

Cell Carcinoma ◽

Disease Progression ◽

Metastatic Renal Cell Carcinoma ◽

Dose Escalation ◽

Renal Cell ◽

Kinase Inhibitor ◽

Drug Label ◽

Entire Cohort

IntroductionThe AXIS trial established axitinib as a standard of care treatment for patients with metastatic renal cell carcinoma (mRCC) after failure of a prior tyrosine kinase inhibitor. Axitinib dosing begins at 5 mg twice daily, with escalation of doses to 7 and 10 mg after consecutive 2-week intervals if tolerated (as per the drug label). Given clinical concerns about drug-related toxicity, we have used a pragmatic strategy where dose escalations were made only after disease progression or where rapid responses were clinically required.MethodsWe performed a retrospective review of electronic health records and radiology of all patients with mRCC treated with axitinib for >2 weeks at Addenbrooke’s Hospital, Cambridge, UK, over a 37 -month period to determine the clinical and radiological effects of dose escalations made according to the above strategy.Results42 patients fitting these criteria were identified, 29 having ≥1 dose escalation event (DEE). 60 DEEs were identified (median of two per patient), and the objective radiological consequences of 53 DEEs could be evaluated. The disease control rate (partial response or stable disease) after the first DEE instituted for disease progression was similar to that after the second DEE (68.8% vs 70%). 56.6 % of all DEEs and 63.6 % of DEEs made as a result of disease progression resulted in disease control. The median OS from the commencement of axitinib for all dose-escalated patients was 19.9 months, and 16.5 months for the entire cohort. The mean dose (for all patients) at 90 days after starting axitinib was 5.92 mg.ConclusionThese data suggest that dose escalation of axitinib after disease progression may be an effective dosing strategy for patients with mRCC, and this may be a preferred option in patients in whom there are particular concerns about drug-related toxicity, quality of life optimisation or healthcare-associated costs.

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How to optimise treatment compliance in metastatic renal cell carcinoma with targeted agents

Annals of Oncology ◽

10.1093/annonc/mdp073 ◽

2009 ◽

Vol 20 ◽

pp. i7-i12 ◽

Cited By ~ 23

Author(s):

A. Ravaud

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Treatment Compliance ◽

Targeted Agents

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A novel strategy for axitinib dosing in the treatment of metastatic renal cell carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.6_suppl.464 ◽

2017 ◽

Vol 35 (6_suppl) ◽

pp. 464-464

Author(s):

Gary Doherty ◽

Deirdre Lynskey ◽

Athena Matakidou ◽

Kate Fife ◽

Tim Eisen

Keyword(s):

Renal Cell Carcinoma ◽

Disease Control ◽

Cell Carcinoma ◽

Disease Progression ◽

Metastatic Renal Cell Carcinoma ◽

Dose Escalation ◽

Survival Data ◽

Renal Cell ◽

Drug Exposure ◽

Dosing Strategy

464 Background: The AXIS trial established axitinib as an effective second line treatment for patients with metastatic renal cell carcinoma (mRCC). The dosing schedule of axitinib in this trial begins at 5mg twice daily, with escalation of individual doses to 7mg and 10mg after consecutive 2 week intervals if tolerated. We observed significant drug-related toxicity using this dosing strategy, particularly after dose escalations, while clinical responses were often observed at the starting dose. We therefore switched to a pragmatic strategy where dose escalations were made only after disease progression or where a rapid response was deemed clinically pertinent. Methods: We performed a retrospective review of electronic health records and radiology of all patients with mRCC treated with axitinib for greater than 2 weeks at Addenbrooke’s Hospital, Cambridge, UK (a tertiary referral center), over a 40 month period to determine the clinical and radiological effects of dose escalations made according to the above strategy. Results: 42 patients fitting these criteria were identified; of these, 29 had at least one dose escalation event (DEE). A total of 58 DEEs were identified, with a median of 2 per patient, and the objective radiological consequences of 50 of these could be determined. The disease control rate (partial response or stable disease) after the first DEE instituted for disease progression was similar to that after the second DEE (68.8% versus 70%). 56% of all DEEs, and 62.5% of DEEs made as a result of disease progression, resulted in disease control. The median overall survival from the commencement of axitinib for all dose-escalated patients was 19.9 months, and 6.7 months for non-dose-escalated patients. The median survival for dose-escalated patients with a higher than median time on a prior tyrosine kinase inhibitor has not been reached at the time of data cut-off. The mean dose (for all patients) at 90 days after starting axitinib was 5.92 mg. Conclusions: These data suggest that dose escalation of axitinib after disease progression may be an effective dosing strategy for patients with mRCC, and may reduce toxicity through lower drug exposure. Our survival data compares favourably to the AXIS trial in a real practice population.

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Inverse association between baseline renal function and overall survival in patients with metastatic renal cell carcinoma who were treated with molecular-targeted agents

Annals of Oncology ◽

10.1093/annonc/mdw373.36 ◽

2016 ◽

Vol 27 ◽

pp. vi282

Author(s):

M. Hiroyuki ◽

H. Miyake ◽

M. Fujisawa

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Renal Function ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Inverse Association ◽

Targeted Agents ◽

Molecular Targeted Agents ◽

Baseline Renal Function

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Treatment patterns: Targeted therapies indicated for first-line management of metastatic renal cell carcinoma in a real-world setting.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.5_suppl.416 ◽

2012 ◽

Vol 30 (5_suppl) ◽

pp. 416-416

Author(s):

Gregory P. Hess ◽

Rohit Borker ◽

Eileen Fonseca

Keyword(s):

Renal Cell Carcinoma ◽

Clinical Practice ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Real World ◽

Renal Cell ◽

Treatment Duration ◽

Treatment Patterns ◽

Targeted Agents ◽

Line Therapy

416 Background: Limited information about real-world treatment patterns of targeted agents for metastatic renal cell carcinoma (mRCC) is available to inform their use in clinical practice. Methods: This retrospective, observational study employed US claims data (January 2007-November 2010) to identify treatment patterns, including treatment duration and dosing, for targeted agents (sunitinib, sorafenib, pazopanib, bevacizumab, and temsirolimus) indicated in 1st line management of advanced/mRCC. The study included adult mRCC patients who were observed for ≥3 months after initiation of their 1st line therapy with a targeted agent. Descriptive analyses were conducted for the observed treatment patterns. Results: A total of 273 patients on 1st line therapy were identified and included in the study sample out of which 235 patients were treated with sunitinib, 16 patients with sorafenib, and 15 patients with temsirolimus. Pazopanib and bevacizumab were excluded from further analysis due to their small samples; n<10. The median observed treatment durations were: sunitinib 3.3 months, sorafenib 4.0 months, and temsirolimus 2.6 months. Patients initiating therapy on sorafenib (n=16) and temsirolimus (n=15) in the study sample were insufficient for meaningful dosing analyses. In sum, of the n=235 sunitinib patients, 178 (approximately 76%) initiated therapy at the indicated dose of 50 mg. Sixty-five percent of these patients were not observed filling a 4th script (the average number observed), while 26% maintained their starting dose and 9% experienced a dose reduction at their fourth fill. (See table). Conclusions: This study suggests that opportunities exist to improve treatment duration in real-world clinical practice and to better understand possible influences, other than disease progression, on treatment and dose changes. [Table: see text]

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