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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
| Study endpoints: | |
|---|---|
| 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).
Inclusion criteria
- 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.
Exclusion criteria
- 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) (n=57) |
Treatment-naïve (cohort C) (n=36) |
|
|---|---|---|
| Age (years) | ||
| 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) (n=57) |
Treatment naïve (cohort C) (n=36) |
|
|---|---|---|
| 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.
References
- 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
