The sample size necessary to demonstrate a statistical superiority, based on the hypothesis that one or both drugs can improve the historically documented PRDFS rate of 12% up to approximately 35%, was estimated to require 18 patients per arm, assuming an alpha error level 5% and a power of 81%.
The evaluation of the primary endpoint PRDFS rate was performed as comparison of the 12-month PRDFS rate with the fixed value of 12% (i.e., the average PRDFS rate after second relapse in historical control groups) using an exact Binomial test .
After one year of treatment PRDFS rate in Viscum arm was 55.6%, compared to historical 12% rate: P = 0.0041; 95% CI (21.2%; 86.3%) (five out of nine patients) and it was 27.3%, P = 0.2724; 95% CI (6.0%; 61.0%) for Etoposide arm (three out of eleven patients) (see Figure 1).
Until July 2013 in the Viscum arm the median PRDFS (including censored dates) is 39 months (range 2-73 months).
The treatment of relapsed osteosarcoma patients is unsatisfactory especially after a second or further relapse because there is no effective adjuvant treatment besides surgery that can prolong PRDFS. In addition to this, heavily pretreated patients often do not want to receive another aggressive treatment with serious side effects.