A new therapeutic opportunity treatment of NSCLC: the BRAF V600 mutation

A new therapeutic opportunity treatment of NSCLC: the BRAF V600 mutation

FDA and EMA approved and reimbursed dabrafenib + trametinib combination therapy for the treatment of adult patients affected by advanced stage of non-small cell lung cancer, BRAF V600 positive.

BRAF gene is mutated in 4% of patients with non-small cell lung cancer (NSCLC). 50% of these patients have the V600E mutation.

BRAF mutations, considered as alternative oncogenic drivers in NSCLC, lead to constitutive activation of cell signaling pathways downstream of MAP kinase, are generally mutually exclusive compared to EGFR mutations and ALK and ROS1 rearrangements and, in contrast to these, are more frequent in smokers. 30% of NSCLC patients BRAF V600E positive show a benefit if treated with a BRAF inhibitor such as vemurafenib or dabrafenib. Data also reveal that combined therapy with BRAF and MEK inhibitors, specifically dabrafenib and trametinib, doubling response rate (66.7% in previously treated patients, 64% in untreated patients) and improved disease-free survival (more than 10 months), as already known for melanoma patients with BRAF V600E mutation. Antitumor activity of dabrafenib-trametinib combinational treatment is comparable to what EGFR or ALK inhibitors shown in NSCLC patients positive respectively to EGFR variants or ALK fusions.

Considering this, FDA and EMA have approved the combination of dabrafenib + trametinib for the treatment of NSCLC advanced patients positive to BRAF V600 mutation. This indication has been implemented last December also by AIFA in Italy and the NHS in UK introducing consequently the reimbursement for patients eligible for treatment.

Further Clinical studies are underway to evaluate the efficacy of other combinations of BRAF- and MEK-inhibitors in patients affected by NSCLC with BRAF mutation already approved for melanoma, as vemurafenib + cobimetinib and encorafenib + binimetinib.

The mutational study of BRAF gene and specifically BRAF V600, already indicated as a predictive marker for colon and melanoma tumors, becomes now an essential tool also for the precision medicine in patients with non-small cell lung cancer (NSLC). BRAF mutations assay can be performed with various analytical methods, including next-generation sequencing (NGS), Mass Spectrometry for nucleic acids (MALDI-TOF), Real-Time PCR and Pyrosequencing.

Diatech Pharmacogenetics purpose a complete portfolio of CE-IVD products dedicated to precision medicine in compliance with international guidelines and recommendations based on NGS, MALDI TOF, RT PCR ad Pirosequencing technologies.

Bibliographic references

  1. Planchard D, Besse B, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously treated BRAF(V600E)-mutant metastatic non-small cell lung cancer: an open-label, multicentre phase 2 trial. Lancet Oncol. 2016;17(7):984–993. doi:10.1016/S1470-2045(16)30146-2
  2. Planchard D, Smit EF, Groen HJM, et al. Dabrafenib plus trametinib in patients with previously untreated BRAFV600E-mutant metastatic non-small-cell lung cancer: an open-label, phase 2 trial. Lancet Oncol. 2017;18(10):1307–1316. doi:10.1016/S1470-2045(17)30679-4
  3. Planchard D, Besse B, Kim TM et al. Updated survival of patients (pts) with previously treated BRAF V600E–mutant advanced non-small cell lung cancer (NSCLC) who received dabrafenib (D) or D + trametinib (T) in the phase II BRF113928 study. Journal of Clinical Oncology 2017 35:15_suppl, 9075-9075
  4. Planchard D, Johnson BE. BRAF Adds an Additional Piece of the Puzzle to Precision Oncology-Based Treatment Strategies in Lung Cancer. Arch Pathol Lab Med. 2018;142(7):796–797. doi:10.5858/arpa.2018-0088-ED
  5. GU Serie Generale n.294 del 16-12-2019
  6. https://www.onclive.com/insights/expanding-targets-nsclc/treatment-options-for-brafmutated-nsclc

 

2020-04-17T16:39:14+00:00