Trametinib (2) – Mekinist®
Non-small cell lung carcinoma (NSCLC), BRAF V600 mutation
Characteristics
| Start date | 01.05.2017 – Marketing authorisation: 27.03.2017 |
|---|---|
| Resolution | 19.10.2017 |
| INN | Trametinib |
| Brand name | Mekinist® |
| Pharm. company | Novartis Pharma GmbH |
| G-BA Procedure ID | D-284 |
| ATC code | L01EE01 MEK inhibitors (L01EE) |
| ICD-10 codes (AIS) | C34.0Malignant neoplasm of carina, C34.1Malignant neoplasm of upper lobe, bronchus or lung, C34.2Malignant neoplasm of middle lobe, bronchus or lung, C34.3Malignant neoplasm of lower lobe, bronchus or lung, C34.8Malignant neoplasm of overlapping sites of bronchus and lung, C34.9Malignant neoplasm of unspecified part of bronchus or lung |
| Alpha-ID codes (AIS) | I111155Carcinoma of the upper lobe bronchus, I116693Non-small cell lung cancer, I24595Carcinoma of the main bronchus, I30015Lung carcinoma of the middle lobe, I30021Lung carcinoma of the lower lobe, I30022Malignant neoplasm of the bronchi and lungs, overlapping several sub-areas |
| DDD | 2 mg O |
| Therapeutic area | Oncological diseases Non-small-cell lung carcinoma (NSCLC) |
| Reason for procedure | New therapeutic indication |
| Specialty | ACT change Combination therapy |
| Therapeutic indication of the resolution |
|---|
|
Trametinib in combination with dabrafenib is indicated for the treatment of adult patients with advanced non-small cell lung cancer with a BRAF V600 mutation. |
| Subpopulation | Indication | Comparator |
|---|---|---|
| 1) | Treatment of adult patients with advanced non-small cell lung cancer with a BRAF V600 mutation: patients without pre-treatment | Patients with ECOG performance status 0, 1 or 2: cisplatin in combination with a third-generation cytostatic (vinorelbine or gemcitabine or docetaxel or paclitaxel or pemetrexed) or carboplatin in combination with a third-generation cytostatic or carboplatin in combination with nab-paclitaxel, patients with ECOG performance status 2: alternatively to platinum-based combination treatment: a monotherapy with gemcitabine or vinorelbine |
| 2a) | Treatment of adult patients with advanced non-small cell lung cancer with a BRAF V600 mutation: patients with pre-treatment for whom therapy with docetaxel or pemetrexed is indicated | Docetaxel or pemetrexed |
| 2b) | Treatment of adult patients with advanced non-small cell lung cancer with a BRAF V600 mutation: patients with pre-treatment for whom therapy with docetaxel or pemetrexed is not indicated | Best-Supportive-Care |
Studies and Results
|
No. of studies
(best subpopulation) |
1 (BRF113928) |
|---|---|
|
Study design
(best subpopulation) |
Single-arm + historical comparison |
|
Meta analysis
(best subpopulation) |
no |
| Reason for dividing into subpopulations (G-BA) | Previous treatment, Patient eligibility |
| ACT change | 19.09.2017 – nach Stellungnahmeverfahren |
- Clinical trials
- A marketing authorisation for Trametinib, in combination with dabrafenib, was granted 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 minor 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 previously treated patients.
- For 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, additional benefit is not proven compared with the appropriate comparator therapy.
Courtesy translation only, please refer to the German original.
Associated procedures
| Trametinib (3) | Mekinist® | Novartis Pharma GmbH | Melanoma, in combination with dabrafenib, BRAF V600 mutation, adjuvant therapy | 1,290–1,590 | 100% Indication of considerable additional benefit | |
| Trametinib (2) | Mekinist® | Novartis Pharma GmbH | Non-small cell lung carcinoma (NSCLC), BRAF V600 mutation | 230–720 | 100% additional benefit not proven | |
| Trametinib (1) | Mekinist® | Novartis Pharma GmbH | Melanoma, BRAF V600 mutation | 1,400 | 50% Indication of considerable additional benefit |
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