Tafinlar + Mekinist is a proven, first-line treatment for NSCLC patients with BRAF+ V600 mutation1–5
The efficacy and safety of Tafinlar in combination with Mekinist was assessed in 171 patients with BRAF V600E mutation-positive NSCLC in a Phase II, multicohort, multicentre, non-randomised, open-label study (NCT01336634). Patients were sequentially enrolled into 3 different cohorts based on the number of prior lines of systemic treatment for metastatic disease.1–3,6,7
|Primary endpoint||Investigator-assessed ORR*|
|Secondary endpoints||PFS, OS, DOR, safety, tolerability and pharmacokinetics|
Adapted from Planchard D, et al. ASCO virtual meeting, May 29-31, 2020. Poster7
*Defined as the percentage of patients who achieved a confirmed complete response or partial response per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1).
- Stage IV NSCLC.
- Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1.
- Presence of BRAF V600E mutation (based on local testing).
- ECOG performance status 0–2.
- Estimated life expectancy of at least 3 months.
Further details on inclusion and exclusion criteria can be found in Planchard et al. 20174 or at https://clinicaltrials.gov/ct2/show/NCT01336634.
- Patients who had received previous BRAF or MEK inhibitor therapy were eligible for enrolment into cohort B, but were excluded from cohort C. Although patients in cohort C could have no previous systemic therapy for metastatic disease, patients who tested positive could have received these agents as adjuvant therapy. This is the major difference between the cohorts.
- Patients with brain metastases were not permitted unless they were asymptomatic, untreated, and measured less than 1 cm, or, if treated, were clinically and radiographically stable 3 weeks after local therapy (which could include surgery or radiotherapy).
- Pregnant women, patients with confirmed hepatitis B or C virus infection, or patients with a history or signs of cardiovascular risk.
- Patients with a history of interstitial lung disease, pneumonitis, or a history of or current evidence of retinal vein occlusion.
Baseline characteristics of pre-treated (cohort B) and treatment-naïve (cohort C) patients5
|Pre-treated (cohort B)
|Treatment-naïve (cohort C)
|Median (range)||64.0 (41–88)||67.0 (44–91)|
|Age group (years), n (%)|
|≥18 to <65||29 (51)||14 (39)|
|≥65||28 (49)||22 (61)|
|Female, n (%)||28 (49)||22 (61)|
|ECOG performance status, n (%)|
|0||17 (30)||13 (36)|
|1||35 (61)||22 (61)|
|2||5 (9)||1 (3)|
|Smoking history, n (%)|
|Never smoked||16 (28)||10 (28)|
|Current smoker||6 (11)||5 (14)|
|Former smoker||35 (61)||21 (58)|
ORR, DOR, PFS and OS for pre-treated (cohort B) and treatment-naïve (cohort C) patients5
|Pre-treated (cohort B)
|Treatment naïve (cohort C)
|ORR% (CR+PR)||68.4% (39)||63.9% (23)|
|mDOR/months||9.8 (6.9–18.3)||10.2 (8.3–15.2)|
|mPFS/months||10.2 (6.9–16.7)||10.8 (7.0–14.5)|
|mOS/months||18.2 (14.3–28.6)||17.3 (12.3–40.2)|
|5-year survival rates||19%||22%|
For more information on Tafinlar + Mekinist please refer to the Summary of Product Characteristics and Patient Information Leaflets.
NSCLC, non-small cell lung cancer; V600E, mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600.
BID, twice daily; CI, confidence interval; DOR, duration of response; ECOG, Eastern Cooperative Oncology Group; IL, first-line; NE, not estimable; NSCLC, non-small cell lung cancer; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; QD, once daily; RECIST, Response Evaluation Criteria in Solid Tumours; V600E, mutation of the BRAF gene in which valine (V) is substituted by glutamic acid (E) at amino acid 600.
- Tafinlar (dabrafenib) Summary of Product Characteristics. Great Britain & Northern Ireland.
- Mekinist (trametinib) Summary of Product Characteristics. Great Britain.
- Mekinist (trametinib) Summary of Product Characteristics. Northern Ireland.
- Planchard D, et al. Lancet Oncol 2017;18:1307–1316.
- Planchard D, et al. J Thorac Oncol 2021;Aug 26:S1556-0864(21)02403-5.
- Clinicaltrials.gov. NCT01336634 Available at: https://clinicaltrials.gov/ct2/show/record/NCT01336634?view=record. [Accessed November 2021].
- Planchard D, et al. ASCO virtual meeting, May 29–31, 2020. Poster