Trial reportCancer medicine2016
Adjusting for treatment switching in the METRIC study shows further improved overall survival with trametinib compared with chemotherapy.
Trial report in Cancer medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Comparative Risks of High-Grade Adverse Events Among FDA-Approved Systemic Therapies in Advanced Melanoma: Systematic Review and Network Meta-Analysis.Frontiers in oncology · 2020Pooled it
- Pooled it
- A systematic review and network meta-analysis of immunotherapy and targeted therapy for advanced melanoma.Cancer medicine · 2017Pooled it
- Amivantamab-Chemotherapy in Non-Small Cell Lung Cancer with EGFR Exon 20 Insertions: Impact of Treatment Crossover and Other Endpoints from the Phase III PAPILLON Study.Targeted oncology · 2025Trial
- Compliance-Adjusted Estimates of Aspirin Effects Among Older Persons in the ASPREE Randomized Trial.American journal of epidemiology · 2023Trial
- Insights adjusting for non-adherence in randomized clinical trials: a reanalysis of an adjuvant trial of tamoxifen duration in early breast cancer.British journal of cancer · 2023Trial
- Adjusting Overall Survival Estimates for Treatment Switching in Metastatic, Castration-Sensitive Prostate Cancer: Results from the LATITUDE Study.Targeted oncology · 2019Trial
- Adjusting for treatment switching in the METRIC study shows further improved overall survival with trametinib compared with chemotherapy.Cancer medicine · 2016Trial
- TOPK Suppresses the CD8Cancer communications (London, England) · 2026Article
- Accounting for extent of non-compliance when estimating treatment effects on an ordinal outcome in randomized clinical trials.BMC medical research methodology · 2025Article
- Unaddressed Challenges in the Treatment of Cutaneous Melanoma?Medicina (Kaunas, Lithuania) · 2024Review
- Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances.International journal of molecular sciences · 2024Review
- Management of Advanced Invasive Melanoma: New Strategies.Advances in therapy · 2023Review
- Assessing the Influence of Subsequent Immunotherapy on Overall Survival in Patients with Unresectable Stage III Non-Small Cell Lung Cancer from the PACIFIC Study.Current therapeutic research, clinical and experimental · 2021Article
- Causal inference for long-term survival in randomised trials with treatment switching: Should re-censoring be applied when estimating counterfactual survival times?Statistical methods in medical research · 2019Article
- Two-stage estimation to adjust for treatment switching in randomised trials: a simulation study investigating the use of inverse probability weighting instead of re-censoring.BMC medical research methodology · 2019Article
- Network Meta-analysis of Progression-Free Survival and Overall Survival in First-Line Treatment of BRAF Mutation-Positive Metastatic Melanoma.Oncology and therapy · 2016Article
- Further Practical Guidance on Adjusting Time-To-Event Outcomes for Treatment Switching.Pharmaceutical statisticsArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trametinib, a selective inhibitor of mitogen-activated protein kinase kinase 1 (MEK1) and MEK2, significantly improves progression-free survival compared with chemotherapy in patients with BRAF V600E/K mutation-positive advanced or metastatic melanoma (MM). However, the pivotal clinical trial permitted randomized chemotherapy control group patients to switch to trametinib after disease progression, which confounded estimates of the overall survival (OS) advantage of trametinib. Our purpose was to estimate the switching-adjusted treatment effect of trametinib for OS and assess the suitability of each adjustment method in the primary efficacy population. Of the patients randomized to chemotherapy, 67.4% switched to trametinib. We applied the rank-preserving structural failure time model, inverse probability of censoring weights, and a two-stage accelerated failure time model to obtain estimates of the relative treatment effect adjusted for switching. The intent-to-treat (ITT) analysis estimated a 28% reduction in the hazard of death with trametinib treatment (hazard ratio [HR], 0.72; 95% CI, 0.52-0.98) for patients in the primary efficacy population (data cut May 20, 2013). Adjustment analyses deemed plausible provided OS HR point estimates ranging from 0.48 to 0.53. Similar reductions in the HR were estimated for the first-line metastatic subgroup. Treatment with trametinib, compared with chemotherapy, significantly reduced the risk of death and risk of disease progression in patients with BRAF V600E/K mutation-positive advanced melanoma or MM. Adjusting for switching resulted in lower HRs than those obtained from standard ITT analyses. However, CI are wide and results are sensitive to the assumptions associated with each adjustment method.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.