Dataset Information

Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial.

ABSTRACT:

Context

Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation.

Objective

The aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas.

Design

PRIMARYS was a 48-week, multicenter, open-label, single-arm study.

Setting

The study was conducted at specialist endocrine centers.

Patients

Treatment-naïve acromegalic patients with GH-secreting macroadenomas participated in the study.

Intervention

Lanreotide Autogel 120 mg was administered sc every 28 days (without dose titration).

Outcome measures

The primary endpoint was the proportion of patients with clinically significant (≥20%) tumor volume reduction (TVR) at week 48/last post-baseline value available using central assessments from three readers. The null hypothesis (H0) for the primary endpoint was that the proportion with TVR was ≤55%. Secondary endpoints included: TVR at other time points, GH and IGF-1, acromegalic symptoms, quality of life (QoL), and safety.

Results

Sixty-four of 90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/last post-baseline value available was achieved by 62.9% (95% confidence interval, 52.0, 72.9) of 89 patients in the primary analysis (intention-to-treat population; H0 not rejected) and 71.9-75.3% in sensitivity (n = 89) and secondary analyses (n = 63) (H0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance.

Conclusions

Primary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor volume, GH and IGF-1, and acromegalic symptoms, and improves QoL.

SUBMITTER: Caron PJ

PROVIDER: S-EPMC4009579 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial.

Caron Philippe J PJ Bevan John S JS Petersenn Stephan S Flanagan Daniel D Tabarin Antoine A Prévost Gaëtan G Maisonobe Pascal P Clermont Antoine A

The Journal of clinical endocrinology and metabolism 20130101 4

<h4>Context</h4>Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation.<h4>Objective</h4>The aim of the study was to better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with GH-secreting macroadenomas.<h4>Design</h4>PRIMARYS was a 48-week, multicenter, open-label, single-arm study.<h4>Setti ...[more]

PMID: 24423301

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Project description:BACKGROUND:Lanreotide autogel is a somatostatin analog (SSA) approved for the treatment of acromegaly in 73 countries worldwide; however, it is not yet approved in China. The aim of this study was to evaluate the efficacy and safety of lanreotide autogel compared with lanreotide 40?mg prolonged release (PR) in Chinese patients with active acromegaly. METHODS:LANTERN was a phase 3, randomized, open-label, non-inferiority study. Patients with active acromegaly who had undergone surgery ?3?months prior, or were unlikely or unable to undergo surgery, were treated with lanreotide autogel 60/90/120?mg (monthly deep subcutaneous injection) or lanreotide 40?mg PR (intramuscular injection every 7, 10, or 14?days) for 32?weeks. Primary endpoint was mean change-from-baseline in age-adjusted insulin-like growth factor-1 (IGF-1) standard deviation scores (SDS) at the end-of-study. Secondary endpoints included: growth hormone (GH) levels ?2.5??g/L or???1.0??g/L, ?20% reduction in tumor volume (TV) and safety. RESULTS:In total, 128 patients were randomized and received study treatment. Lanreotide autogel was non-inferior to lanreotide 40?mg PR: treatment difference (95% CI) for IGF-1 SDS between groups was -?0.32 (-?0.74, 0.11; per protocol population) and?-?0.27 (-?0.63, 0.09; intention-to-treat [ITT] population), respectively. Reductions in IGF-1 (-?6.453 vs -?7.003) and GH levels (-?9.548??g/L vs -?13.182??g/L), and the proportion of patients with ?1 acromegaly symptom (-?20.3% vs -?32.5%) were observed from baseline to end-of-study in lanreotide autogel and lanreotide 40?mg PR groups, respectively. In the lanreotide autogel group, 45.5% (25/55) patients achieved ?20% reduction in TV compared with 50.9% (25/53) in lanreotide 40?mg PR group (ITT). Safety profiles were similar in both treatment groups. CONCLUSIONS:Lanreotide autogel was non-inferior to lanreotide 40?mg PR in Chinese patients with active acromegaly after 32?weeks of treatment. TRIAL REGISTRATION:Retrospectively registered on ClinicalTrials.gov: NCT02493517 (9 July 2015); prospectively registered on chinadrugtrials.org.cn: CTR20140698 (24 October 2014).

Project description:IntroductionTumor quantity while receiving cancer therapy is the sum of simultaneous regression of treatment-sensitive and growth of treatment-resistant fractions at constant rates. Exponential rate constants for tumor regression/decay (d) and growth (g) can be estimated. Previous studies established g as a biomarker for overall survival; g increases after treatment cessation, can estimate doubling times, and can assess treatment effectiveness in small cohorts by benchmarking to large reference data sets. Using this approach, we analyzed data from the clinical trial CLARINET, evaluating lanreotide depot/autogel 120 mg/4 weeks (LAN) for treatment of neuroendocrine tumors (NETs).Methods and materialsComputed tomography imaging data from 97 LAN- and 101 placebo-treated patients from CLARINET were analyzed to estimate g and d.ResultsData from 92% of LAN- and 94% of placebo-treated patients could be fit to one of the equations to derive g and d (p < .001 in most data sets). LAN-treated patients demonstrated significantly slower g than placebo recipients (p = .00315), a difference of 389 days in doubling times. No significant difference was observed in d. Over periods of LAN administration up to 700 days, g did not change appreciably. Simulated analysis with g as the endpoint showed a sample size of 48 sufficient to detect a difference in median g with 80% power.ConclusionAlthough treatment of NETs with LAN can affect tumor shrinkage, LAN primarily slows tumor growth rather than accelerates tumor regression. Evidence of LAN efficacy across tumors was identified. The growth-retarding effect achieved with LAN was sustained for a prolonged period of time.Implications for practiceThe only curative treatment for neuroendocrine tumors (NETs) is surgical resection; however, because of frequent late diagnosis, this is often impossible. Because of this, treatment of NETs is challenging and often aims to reduce tumor burden and delay progression. A novel method of analysis was used to examine data from the CLARINET trial, confirming lanreotide depot/autogel is effective at slowing tumor growth and extending progression-free survival. By providing the expected rate and doubling time of tumor growth early in the course of treatment, this method of analysis has the potential to guide physicians in their management of patients with NETs.

Project description:INTRODUCTION:Although the previous lanreotide autogel/depot syringe had been well received, feedback indicated that improvements could be made to make it more user-friendly. Additionally, the view that patients should have greater involvement in the research and development process is echoed by the International Neuroendocrine Cancer Alliance. A series of studies aimed to develop and validate a new syringe that works better for patients, caregivers and healthcare professionals (HCPs) by involving these groups at key stages in the development and testing process. METHODS:The multicentre, international, human factor studies, consisted of four formative studies and one validation study. The formative studies collected patient, caregiver and HCP feedback on the lanreotide autogel/depot syringe on the market at the time, and on newly designed prototypes. The validation study was conducted to evaluate the final syringe to confirm that it can be used effectively and safely in the intended environment, by the intended user, for the intended purpose. RESULTS:Overall, 213 individuals participated in the studies; 145 contributed to the formative studies and 68 to the validation study. The validated new-generation syringe included several important updates compared with the lanreotide autogel/depot syringe currently on the market, including the flanges, which are now larger and have a better grip; the overcap, which is white, ridged, opaque and bigger; the plunger supports and the thermoformed tray. No participant hurt themselves or others during the validation study (although several misuses were reported), and all participants succeeded in delivering a complete dose and activating the safety system. CONCLUSION:With collaboration, a new syringe was developed to meet the needs of patients, caregivers and HCPs, whilst ensuring lanreotide was delivered effectively and safely. These studies highlight the importance of involving patients, caregivers and HCPs in clinical evaluation studies to develop medical products that address their concerns and meet their needs. FUNDING:Ipsen. Plain language summary available for this article.

Dataset Information

Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial.

Context

Objective

Design

Setting

Patients

Intervention

Outcome measures

Results

Conclusions

Publications

Tumor shrinkage with lanreotide Autogel 120 mg as primary therapy in acromegaly: results of a prospective multicenter clinical trial.

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