Staburo Wiesn Workshop

It is a very nice custom to have our Staburo statistics training session on the first Monday of the two-week Oktoberfest period. This year, the Staburo team had the chance to learn about the “Comparison of adaptive enrichment designs in clinical trials”. In the second talk, useful insights into cluster analysis were presented. “The cross-validated treatment effect for data-driven subgroup selection algorithms” was the third presentation and rounded up this very informative workshop. As always, this was a great opportunity to share knowledge with the whole Staburo team and we had a very good Q&A session afterwards. Contents of the workshop will be published here, soon.

The second important custom is to pay the Oktoberfest (or also called “Wiesn”) a visit after the workshop. Once again, we had a wonderful time with the team and long-time Staburo clients. We even topped the (by some nerdy team members with a complicated formula) estimated beer consumption – some say due to semi-transparent accounting on the waiters’ side, some think due to thirst. Everyone got home safely – with additional knowledge from the workshop and positive vibes from the Oktoberfest. We are already looking forward to the Staburo “Wiesn” Workshop 2019 and thank all participants for making this a great team event!

Biomarker analyses published in JAMA Oncology

Staburo supported biomarker analyses for a phase III lung-cancer trial. The paper, which was recently published in JAMA Oncology, is a retrospective analysis to assess the association of ErbB mutations with clinical efficacy. Statistical analyses include the identification of predictive and prognostic biomarkers, and the evaluation of their impact using standardized effect plots.

Highlights of the study:

DESIGN, SETTING, AND PARTICIPANTS:

Ad hoc secondary analysis of the LUX-Lung 8 trial, conducted at 183 centers in 23 countries from March 30, 2012, to January 30, 2014. Eligible patients had stage IIIB or IV lung squamous cell carcinoma, with progressive disease after 4 or more cycles of platinum-based chemotherapy.

MAIN OUTCOMES AND MEASURES:

Overall survival, PFS, pooled and individual ERBB gene mutations, ERBB copy number alterations, and EGFR expression.

RESULTS:

Tumor specimens from 245 patients were eligible for next-generation sequencing (TGA subset: 132 patients treated with afatinib; 113 patients treated with erlotinib). In this population, outcomes were improved with afatinib vs erlotinib treatment (PFS: median, 3.5 vs 2.5 months; hazard ratio [HR], 0.69; 95% CI, 0.51-0.92; P = .01; OS: median, 8.4 vs 6.6 months; HR, 0.81; 95% CI, 0.62-1.05; P = .12). Of 245 patients in the TGA subset, 53 (21.6%) had tumors with 1 or more ERBB mutations. Among afatinib-treated patients, PFS (median, 4.9 vs 3.0 months; HR, 0.62; 95% CI, 0.37-1.02; P = .06) and OS (median, 10.6 vs 8.1 months; HR, 0.75; 95% CI, 0.47-1.17; P = .21) were longer among those with ERBB mutation–positive disease than among those without. The presence of HER2 mutations was associated with favorable PFS and OS following afatinib vs erlotinib treatment. There was no apparent association between copy number alteration or EGFR expression level and outcome.

CONCLUSIONS AND RELEVANCE:

Next-generation sequencing may help identify patients with lung squamous cell carcinoma who would derive additional benefit from treatment with afatinib. The role of ERBB mutations, particularly HER2 mutations, as predictive biomarkers for afatinib treatment in this setting warrants further evaluation.

You can find the full publication here:

Goss, Glenwood D., et al. “Association of ERBB mutations with clinical outcomes of afatinib-or erlotinib-treated patients with lung squamous cell carcinoma: secondary analysis of the LUX-Lung 8 randomized clinical trial.” JAMA oncology (2018).

https://jamanetwork.com/journals/jamaoncology/fullarticle/2684635

Staburo contributed to publication in the Journal of Cardiovascular Pharmacology and Therapeutics

Staburo could show, once again, its state-of-the-art biostatistics expertise, by supporting this scientific publication. Here, you find a short summary about the study.

Summary

Dabigatran etexilate is an oral direct thrombin inhibitor. Dabigatran excretion is 80% renal, so exposure increases
with severity of renal failure, which can lead to more adverse events (AE). The FDA approved dabigatran etexilate 75 mg twice daily (BID) for patients with nonvalvular atrial fibrillation (NVAF) having severely impaired renal function (creatinine clearance: 15-30 mL/min), based on post-hoc pharmacokinetic modeling and not based on results of a clinical trial for this population. In this trial, we assessed dabigatran exposure at trough and peak levels in patients with NVAF and severely impaired renal function and compared the result with predictions from PK model.

Methods

Patients received dabigatran etexilate (75 mg BID) for 7 days before blood sampling; Steady-state pre-dose concentration (trough) and steady-state peak concentration were taken. Pharmacodynamic parameters at baseline were assessed by established coagulation assays.

Results

Of 60 treated patient, 40% were male and 78.3% were white; median age was 84 years. Steady-state pre-dose concentration values were close to pharmacokinetic modeling predictions with a geometric mean (gMean) of 155 ng/mL, geometric coefficient of variation (gCV) of 76.9%, and range of 15.6 to 498 ng/mL. The Steady-state post-dose peak had a gMean of 202 ng/mL, gCV of 70.6%, and range of 42.0 to 680 ng/mL. Pharmacodynamic effects on coagulation paralleled dabigatran concentrations. Eleven (18.3%) patients had at least one AE; pharmacokinetic results for these patients versus those without AE showed higher trough and peak values. All bleeding events were considered minor by the investigators.

Conclusion

Dabigatran exposure levels largely confirmed earlier pharmacokinetic predictions, supporting the use of dabigatran etexilate 75 mg BID in patients with NVAF and severely impaired renal function. Pharmacodynamic results were also in agreement with earlier studies.

Click here for the abstract on the publication website.

AGAH Workshop ‘Applied course Biostatistics’ on November 7-8, 2018 in Oberursel, Germany

Staburo Managing Directors Dr. Hannes Buchner and Josef Höfler will talk at the AGAH ‘Applied course Biostatistics’ workshop and will provide deeper insights into biostatistics in clinical trials.

The workshop will give the attendees an overview of relevant statistics aspects, like data structures, principles of descriptive statistics and also basic concepts of hypothesis testing. Furthermore, sample size estimation and statistical implications of study designs in phase I trials will be explained during the talks.

The workshop is targeted for project managers, investors and other participants, which are responsible for clinical pharmacology trials. There will be practical examples and scientific presentations, that help the attendees to facilitate the communication with their biostatistics colleagues or service providers, and to interpret the obtained clinical data in a professional way.

The two-day workshop contains an exciting program of lectures and exercises prepared for the participants. There will be presentations from Staburo Managing Directors Dr. Hannes Buchner and Josef Höfler on the second day of the workshop. We are looking forward to the event and to sharing our biostatistics expertise!

Check out the program here and register today!

Staburo’s statistical support in prospective oncology study

Staburo provided statistical support for a prospective study that was recently published in a poster of the LMU Haunersches Kinderspital. The poster describes a double-blinded trial with 26 children and adolescents with cancer, under chemotherapy, testing high-energy commercially available drinks. The rationale of this study was the fact that patients, especially children, under chemotherapy can sometimes not reach the required energy uptake, and nonetheless don´t like the available drinks and refuse them. The prospective study aimed to examine the taste preference of commercially available oral nutritional supplements in Germany. The result was that an energy drink with strawberry flavor and cacao were the best accepted drinks. A consequence of the findings in this study could be to enrich cacao with the unflavored supplement Energea P for a higher energy uptake.

Since the Staburo team not only possesses statistical, but also cinematic expertise, a continuation of the Staburo movie night was long overdue. After some lively discussions and several voting rounds on a Friday 13th, our team welcomed the weekend with pizza, cold drinks and the highly sophisticated horror comedy “Tucker and Dale versus Evil”. Thanks to all who took part and made it such fun – next time maybe with a real horror movie or the all-time favorite Coen brothers classic!