Dataset Information

Everolimus and sunitinib for advanced pancreatic neuroendocrine tumors: a matching-adjusted indirect comparison.

ABSTRACT:

Background

Everolimus and sunitinib have been approved for the treatment advanced pancreatic neuroendocrine tumors, but have not been compared to each other in a randomized trial and have not demonstrated prolonged overall survival compared to placebo. This study aimed to indirectly compare overall and progression-free among everolimus, sunitinib and placebo across separate randomized trials.

Methods

A matching adjusted indirect comparison was conducted in which individual patient data from the pivotal trial of everolimus (n?=?410) were adjusted to match the inclusion criteria and average baseline characteristics reported for the pivotal trial of sunitinib (n?=?171). Prior to matching, trial populations differed in baseline performance status and prior treatments. After matching, these and all other available baseline characteristics were balanced between trials.

Results

Compared to the placebo arm in the sunitinib trial, everolimus was associated with significantly prolonged overall survival (HR?=?0.61, 95% CI?=?0.38-0.98, p?=?0.042).Compared to sunitinib, everolimus was associated with similar progression-free (hazard ratio for death (HR)?=?0.84, 95% CI?=?0.46-1.53, p?=?0.578) and overall survival (HR?=?0.81, 95% CI?=?0.49-1.31, p?=?0.383).

Conclusion

After adjusting for observed cross-trial differences, everolimus treatment was associated with longer overall survival than the placebo arm in the sunitinib trial for advanced pancreatic neuroendocrine tumors.

SUBMITTER: Signorovitch J

PROVIDER: S-EPMC4175512 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Publications

Everolimus and sunitinib for advanced pancreatic neuroendocrine tumors: a matching-adjusted indirect comparison.

Signorovitch James J Swallow Elyse E Kantor Evan E Wang Xufang X Klimovsky Judith J Haas Tomas T Devine Beth B Metrakos Peter P

Experimental hematology & oncology 20131206 1

<h4>Background</h4>Everolimus and sunitinib have been approved for the treatment advanced pancreatic neuroendocrine tumors, but have not been compared to each other in a randomized trial and have not demonstrated prolonged overall survival compared to placebo. This study aimed to indirectly compare overall and progression-free among everolimus, sunitinib and placebo across separate randomized trials.<h4>Methods</h4>A matching adjusted indirect comparison was conducted in which individual patient ...[more]

PMID: 24314093

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Project description:BackgroundAnchored covariate-adjusted indirect comparisons inform reimbursement decisions where there are no head-to-head trials between the treatments of interest, there is a common comparator arm shared by the studies, and there are patient-level data limitations. Matching-adjusted indirect comparison (MAIC), based on propensity score weighting, is the most widely used covariate-adjusted indirect comparison method in health technology assessment. MAIC has poor precision and is inefficient when the effective sample size after weighting is small.MethodsA modular extension to MAIC, termed two-stage matching-adjusted indirect comparison (2SMAIC), is proposed. This uses two parametric models. One estimates the treatment assignment mechanism in the study with individual patient data (IPD), the other estimates the trial assignment mechanism. The first model produces inverse probability weights that are combined with the odds weights produced by the second model. The resulting weights seek to balance covariates between treatment arms and across studies. A simulation study provides proof-of-principle in an indirect comparison performed across two randomized trials. Nevertheless, 2SMAIC can be applied in situations where the IPD trial is observational, by including potential confounders in the treatment assignment model. The simulation study also explores the use of weight truncation in combination with MAIC for the first time.ResultsDespite enforcing randomization and knowing the true treatment assignment mechanism in the IPD trial, 2SMAIC yields improved precision and efficiency with respect to MAIC in all scenarios, while maintaining similarly low levels of bias. The two-stage approach is effective when sample sizes in the IPD trial are low, as it controls for chance imbalances in prognostic baseline covariates between study arms. It is not as effective when overlap between the trials' target populations is poor and the extremity of the weights is high. In these scenarios, truncation leads to substantial precision and efficiency gains but induces considerable bias. The combination of a two-stage approach with truncation produces the highest precision and efficiency improvements.ConclusionsTwo-stage approaches to MAIC can increase precision and efficiency with respect to the standard approach by adjusting for empirical imbalances in prognostic covariates in the IPD trial. Further modules could be incorporated for additional variance reduction or to account for missingness and non-compliance in the IPD trial.

Project description:BackgroundFor nonmetastatic castration-resistant prostate cancer (nmCRPC), 3 drugs under patent protection-apalutamide, enzalutamide, and darolutamide-were approved based on randomized, placebo-controlled trials; 1 drug with generic availability, abiraterone acetate, showed efficacy in a single-arm trial and is commonly prescribed. Lacking head-to-head trials, the optimal treatment for nmCRPC is unknown, despite widely varied treatment costs. We compared the efficacy and safety of nmCRPC treatments.MethodsWe searched bibliographic databases, regulatory documents, and trial registries for nmCRPC trials. We included published results and, when available, original data. We performed matching-adjusted indirect comparison and network meta-analysis and compared treatments regarding metastasis-free survival, overall survival, and serious adverse events.ResultsWe analyzed 5 trials with 4360 participants. Compared with placebo, abiraterone acetate engendered the lowest hazard of metastasis and death (hazard ratio [HR] = 0.22, 95% credible interval [CrI] = 0.12-0.41), followed by apalutamide (HR = 0.28, 95% CrI = 0.23-0.34), enzalutamide (HR = 0.30, 95% CrI = 0.25-0.36), and darolutamide (HR = 0.41, 95% CrI = 0.34-0.49); darolutamide led to the lowest hazard of death (HR = 0.69, 95% CrI = 0.53-0.90), followed by enzalutamide (HR = 0.73, 95% CrI = 0.61-0.87) and apalutamide (HR = 0.75, 95% CrI = 0.59-0.95); darolutamide resulted in the lowest odds of serious adverse events (odds ratio [OR] = 1.32, 95% CrI = 1.02-1.70), followed by enzalutamide (OR =1.43, 95% CrI = 1.08-1.89), apalutamide (OR = 1.58, 95% CrI = 1.23-2.03), and abiraterone acetate (OR = 1.94, 95% CrI = 1.17-3.22).ConclusionsFor nmCRPC, darolutamide offered optimal efficacy and safety among approved drugs, and abiraterone acetate may offer comparable metastasis-free survival benefit with cost savings from generic availability. Future research is needed to more fully examine the benefit of abiraterone acetate.

Dataset Information

Everolimus and sunitinib for advanced pancreatic neuroendocrine tumors: a matching-adjusted indirect comparison.

Background

Methods

Results

Conclusion

Publications

Everolimus and sunitinib for advanced pancreatic neuroendocrine tumors: a matching-adjusted indirect comparison.

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