First interim analysis of a randomised trial of whole brain radiotherapy in melanoma brain metastases confirms high data quality

Abstract

BackgroundBrain metastases are a common cause of death in patients with melanoma. The role of adjuvant whole brain radiotherapy (WBRT) following local treatment of intracranial melanoma metastases is controversial. The Australian and New Zealand Melanoma Trials Group (ANZMTG) and the Trans-Tasman Radiation Oncology Group (TROG) are leading the first ever single histology randomised trial investigating this question. The primary endpoint is distant intracranial failure on magnetic resonance imaging (MRI) within twelve months of randomisation. The first planned interim analysis was performed twelve months after randomisation of the 100th patient. The analysis was an opportunity to review completeness of the trial data to date.MethodsAll data received up to the end of twelve months after randomisation of the 100th patient was reviewed.ResultsReview of pathology reports confirmed that all 100 patients had stage IV melanoma and were appropriately entered into the study. Of the 47 distant intracranial events, 34 occurred in isolation (i.e. only distant failure was identified), whilst 13 were accompanied by local failure. Data review showed compliance with the protocol mandated MRI schedule and accuracy of intracranial failure reporting was very high. The Quality of Life (QoL) component of the study achieved a 91% completion rate. For the neurocognitive function (NCF) assessments, a high completion rate was maintained throughout the 12 month period. Where assessments were not performed at expected time points, valid reasons were noted. Radiotherapy quality was high. Of 50 patients who received WBRT, 32 were reviewed as per protocol design and there was only one major variation out of 308 data points reviewed (0.3%). There were minimal trial related adverse events (AEs) and no serious adverse events (SAEs). Pre-specified protocol stopping rules were not met.ConclusionsThe Data Safety Monitoring Committee (DSMC) recommended the trial continue recruitment after reviewing the unblinded data. The data provision and quality to date indicates that a reliable outcome will be obtained when the final analysis is performed. Accrual is ongoing with 156 out of 200 patients randomised to date (26th November 2014).

Activity and safety of radiotherapy with anti-PD-1 drug therapy in patients with metastatic melanoma

“…Rates of low-grade toxicities following WBRT including headaches, nausea, and radiation dermatitis were as expected when compared the prior published data [19][20][21] (Table 4). Clinically significant cognitive changes were observed in two patients (10%), neither of whom had hippocampal sparing due to the extent of disease.…”

Debate: adjuvant whole brain radiotherapy or not? More data is the wiser choice

“…It has accrued 179 of a required 200 to date. Interim analysis has shown the collected data is of high quality [ 19 ]. However, trial accrual is decreasing as investigators are not offering the trial because of the ASTRO recommendation.…”

A phase 2 study of radiosurgery and temozolomide for patients with 1 to 4 brain metastases

“…The primary study endpoint was (metachronous brain metastases) 8, 10. Secondary endpoints included toxicity, overall survival, and quality of life as measured by Functional Assessment of Cancer Therapy-Brain.…”

“…The primary study endpoint was (metachronous brain metastases). 8 , 10 Secondary endpoints included toxicity, overall survival, and quality of life as measured by Functional Assessment of Cancer Therapy-Brain. Clinical, MRI scans, and quality of life assessments were performed after radiosurgery at 1, 3, 6, 9, 12, 15, 18, 21, and 24 months.…”