Prescribing information

 

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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

 

Schematic showing the study design for the non-small cell lung cancer pivotal trial for Tafinlar and Mekinist. Also table underneath showing study endpoints. 5. Coloured text boxes conteining inclusion and exclusion study criteria.

 

 

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.

GB & NI SmPC for Tafinlar

GB SmPC for Mekinist

NI SmPC for Mekinist

GB & NI PIL for Tafinlar

GB PIL for Mekinist

NI PIL for Mekinist

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

  1. Tafinlar (dabrafenib) Summary of Product Characteristics. Great Britain & Northern Ireland.
  2. Mekinist (trametinib) Summary of Product Characteristics. Great Britain.
  3. Mekinist (trametinib) Summary of Product Characteristics. Northern Ireland.
  4. Planchard D, et al. Lancet Oncol 2017;18:1307–1316.
  5. Planchard D, et al. J Thorac Oncol 2021;Aug 26:S1556-0864(21)02403-5.
  6. Clinicaltrials.gov. NCT01336634 Available at: https://clinicaltrials.gov/ct2/show/record/NCT01336634?view=record. [Accessed November 2021].
  7. Planchard D, et al. ASCO virtual meeting, May 29–31, 2020. Poster
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UK | November 2021 | 167735
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