Dataset Information

Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma.

ABSTRACT:

Background

We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials.

Methods

Patients ?18 years received oral sunitinib 50?mg per day on a 4-weeks-on-2-weeks-off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice.

Results

A total of 4543 patients received sunitinib. Median treatment duration and follow-up were 7.5 and 13.6 months. Objective response rate was 16% (95% confidence interval (CI): 15-17). Median progression-free survival (PFS) and overall survival (OS) were 9.4 months (95% CI: 8.8-10.0) and 18.7 months (95% CI: 17.5-19.5). Median PFS in subgroups of interest: aged ?65 years (33%), 10.1 months; Eastern Cooperative Oncology Group performance status ?2 (14%), 3.5 months; non-clear cell histology (12%), 6.0 months; and brain metastases (7%), 5.3 months. OS was strongly associated with the International Metastatic Renal-Cell Carcinoma Database Consortium prognostic model (n=4065). The most common grade 3/4 treatment-related adverse events were thrombocytopenia (10%), fatigue (9%), and asthenia, neutropenia, and hand-foot syndrome (each 7%).

Conclusion

Final analysis of the sunitinib expanded-access trial provided a good opportunity to evaluate the long-term side effects of a tyrosine kinase inhibitor used worldwide in mRCC. Efficacy and safety findings were consistent with previous results.

SUBMITTER: Gore ME

PROVIDER: S-EPMC4647545 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Publications

Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma.

Gore M E ME Szczylik C C Porta C C Bracarda S S Bjarnason G A GA Oudard S S Lee S-H SH Haanen J J Castellano D D Vrdoljak E E Schöffski P P Mainwaring P P Hawkins R E RE Crinò L L Kim T M TM Carteni G G Eberhardt W E E WE Zhang K K Fly K K Matczak E E Lechuga M J MJ Hariharan S S Bukowski R R

British journal of cancer 20150618 1

<h4>Background</h4>We report final results with extended follow-up from a global, expanded-access trial that pre-regulatory approval provided sunitinib to metastatic renal cell carcinoma (mRCC) patients, ineligible for registration-directed trials.<h4>Methods</h4>Patients ⩾18 years received oral sunitinib 50 mg per day on a 4-weeks-on-2-weeks-off schedule. Safety was assessed regularly. Tumour measurements were scheduled per local practice.<h4>Results</h4>A total of 4543 patients received suniti ...[more]

PMID: 26086878

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Project description:BACKGROUND:Sunitinib is an approved treatment for metastatic renal cell carcinoma (mRCC). The safety profile and efficacy of sunitinib were confirmed in a global expanded access trial (ClinicalTrials.gov identifier: NCT00130897). This report presents a subanalysis of the final trial data from patients in Latin America. METHODS:Treatment-naïve or previously treated mRCC patients aged ?18 years received oral sunitinib at a starting dose of 50 mg/day on a 4-weeks-on/2-weeks-off schedule. Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Safety was assessed regularly, and tumor measurements were scheduled per local practice (using Response Evaluation Criteria in Solid Tumors). RESULTS:In total, 348 patients from Latin America received sunitinib. Overall, 75% of patients had two or more sites of metastatic disease, 28% were aged ?65 years, 14% had an Eastern Cooperative Oncology Group performance status ?2, 9% had brain metastases, 9% had no prior nephrectomy, and 5% had non-clear cell RCC. Median treatment duration was 8 months, and median follow-up was 15.1 months. In total, 326 patients (94%) discontinued treatment, primarily due to death (41%) or lack of efficacy (22%). Most treatment-related adverse events were of mild to moderate severity (grade 1/2). Mucosal inflammation (reported in 54% of patients), diarrhea (53%), and asthenia (41%) were the most common any-grade treatment-related adverse events. Asthenia (12%), neutropenia (10%), and fatigue and thrombocytopenia (both 9%) were the most common grade 3/4 treatment-related adverse events. In total, 311 patients were included for tumor response, of whom eight (3%) had a complete response and 46 (15%) a partial response, yielding an objective response rate of 17%. Median duration of response, progression-free survival, and overall survival were 26.7, 12.1, and 16.9 months, respectively. CONCLUSION:The efficacy and safety profile of sunitinib in patients with mRCC from Latin America was comparable to that in the entire cohort of the global expanded access trial.

Project description:BackgroundMetastatic renal cell carcinoma (mRCC) patients receiving first-line sunitinib typically survive >2 yr, with chronic treatment sometimes extending to ≥6 yr.ObjectiveTo analyze long-term safety with sunitinib in mRCC patients.Design, setting, and participantsData were pooled from 5739 patients in nine trials, comprising seven phase II studies, a phase III study, and an expanded-access trial in various treatment settings (e.g., cytokine refractory or treatment-naïve).Outcome measurements and statistical analysisInterval and cumulative time-period analyses evaluated the incidence of treatment-related adverse events (TRAEs) for up to 6 yr, in the overall population and in those with long-term (≥2 yr) sunitinib treatment.Results and limitationsAmong long-term patients (n=807), most TRAEs occurred initially in the first year and then decreased in frequency; TRAEs following this pattern included decreased appetite, diarrhea, dysgeusia, dyspepsia, fatigue, hypertension, mucosal inflammation, nausea, and stomatitis. However, hypothyroidism increased by interval analysis from 6% at 0-<6 mo to 42% at 5-<6 yr and by cumulative analysis from 14% at 0-<1 yr to 36% over 6 yr. Grade 3/4 TRAEs in long-term patients peaked during the first year and then steadily decreased. The overall population displayed only minor differences from long-term patients, with no clinically significant differences between grade ≥3 TRAE profiles (<5% difference in incidence rates at all intervals). Limitations included retrospective design, assessment variability, lack of pharmacokinetic data, and absence of baseline characteristics for long-term patients.ConclusionsProlonged sunitinib was not associated with new types or increased severity of TRAEs. Except hypothyroidism, toxicity was not cumulative.Patient summaryMore than 800 mRCC patients received sunitinib for between 2 and 6 yr without experiencing new or more severe treatment-related toxicity. Clinicians may be able to prescribe chronic sunitinib treatment for as long as patients continue to derive clinical benefit, without untoward additional risk.

Project description:Following approval of the oral, multitargeted tyrosine kinase inhibitor sunitinib malate for the treatment of patients with metastatic renal cell carcinoma (mRCC) in Europe and the USA in 2006, the agent has had a substantial impact on the treatment landscape in this setting. Sunitinib is now recommended in international treatment guidelines for the first-line treatment of favourable- or intermediate-risk mRCC and as an alternative option in poor-risk mRCC. In the 6 years since the approval of sunitinib, the range of agents available for the treatment of mRCC has expanded substantially, and this, together with a number of additional therapies in late-stage development, has increased the treatment options available to patients. Results from a phase III trial and a global expanded access study have provided robust data to support the efficacy of sunitinib in mRCC, including in real-world populations. Data also suggest a significant quality of life benefit with sunitinib, with superior patient-reported outcomes observed with this agent compared with interferon-α therapy. Both clinical and real-world study data also support the safety profile of sunitinib; most treatment-associated adverse events are mild to moderate in severity and can be managed effectively with close monitoring and proactive management. Clinical experience with sunitinib has demonstrated that therapy management, involving optimal dosing, maximum treatment duration and prompt and effective adverse event management, supports optimal patient outcomes with sunitinib. In this review we discuss clinical experience with sunitinib in mRCC, with an emphasis on real-world data, and utilize clinical case studies to examine the successful implementation of therapy management strategies for optimal patient outcomes. An increasing body of evidence suggests that side effects associated with sunitinib therapy, including hypertension, hand-foot syndrome and hypothyroidism, may represent effective markers of treatment response, and these will also be discussed.

Dataset Information

Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma.

Background

Methods

Results

Conclusion

Publications

Final results from the large sunitinib global expanded-access trial in metastatic renal cell carcinoma.

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