Dabrafenib (3) – Tafinlar®

• Clinical trials
  • Dabrafenib, in combination with trametinib, was granted a marketing authorisation on the basis of results from the non-randomised, open-label study BRF113928.

1) Patients who have not received prior treatment

• For patients with advanced non-small cell lung cancer harbouring a BRAF V600 mutation who have not received prior treatment, an additional benefit over the appropriate comparator therapy is not proven.
• For the trametinib plus dabrafenib arm, Cohort C of the BRF113928 study was used.
• In particular, the data on overall survival submitted by the pharmaceutical manufacturer have limited statistical significance due to the small number of patients studied and are therefore not suitable for inferring any additional benefit of trametinib in combination with dabrafenib for untreated patients.
• The determination of the median overall survival in Cohort C of the BRF113928 study is based on data from 36 patients; for the comparative studies, data from 12 (Cardarella 2013), 28 (Ding 2017) and 22 (NGM Cologne 2017) patients were included in the analyses.
• Although there is a numerical doubling of the median survival time, the median overall survival from the Ding 2017 study falls within the confidence interval of the survival time calculated from the data of the BRF113928 study, and the confidence intervals of the BRF113928 study and the NGM Cologne study overlap.
• Furthermore, analyses of the IFCT study cited in support of the EPAR show a median overall survival for patients with BRAF V600-positive NSCLC receiving standard therapy that is comparable to the results of the BRF113928 study.
• Furthermore, the study populations considered are not sufficiently comparable.

2a) Patients with prior treatment – a. For whom treatment with docetaxel or pemetrexed is indicated

• For patients with advanced non-small cell lung cancer harbouring a BRAF V600 mutation who have received prior treatment and for whom treatment with docetaxel or pemetrexed is indicated, an additional benefit over the appropriate comparator therapy is not proven.
• For trametinib plus dabrafenib, the pharmaceutical manufacturer refers to Cohort B of the BRF113928 study, which included 57 pre-treated patients.
• For the comparison, results from five previously treated patients from the 2017 NGM Cologne registry analysis are presented.
• The data from five pre-treated patients do not allow for a valid conclusion regarding the additional benefit of trametinib plus dabrafenib.

2b) Pre-treated patients – b. For whom treatment with docetaxel and pemetrexed is not indicated

• For patients with advanced non-small cell lung cancer harbouring a BRAF V600 mutation who have received prior treatment and for whom treatment with docetaxel and pemetrexed is not indicated, an additional benefit is not proven compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.