Dabrafenib Shows Promising Results in Non-Small-Cell Lung Cancer

Dabrafenib Shows Promising Results in Non-Small-Cell Lung Cancer

shutterstock_212432119During the European Society for Medical Oncology (ESMO) 2014 Congress held in Madrid in September, two studies were presented concerning promising therapies against subsets of Non-Small-Cell Lung Cancer (NSCLC).

The study entitled “Dabrafenib anti-tumour activity in BRAF V600E mutation-positive non-small cell lung cancer“, present by Dr. David Planchard, pulmonary oncologist at the Gustav-Roussy Cancer Campus, Paris, France, showed that the BRAF inhibitor dabrafenib, had significant anti-tumour activity in patients with advanced BRAF V600E mutant non-small cell lung cancer whose disease had progressed after chemotherapy.

This was an open-label phase II study which enrolled 78 patients diagnosed with BRAF V600E mutant non-small cell lung cancer, treated with dabrafenib alone (150 mg, twice a day). Researchers observed that patients who had received one or more treatments showed an overall response rate of 32%, and after 12 weeks of treatment had a disease control rate of 56%. The median duration of response was 11.8 months, and among the six first-line patients, three of them had partial response to the treatment. Notably, due to the efficacy and safety results obtained in this study, dabrafenib received a Breakthrough Therapy designation in lung cancer from the U.S. Food and Drug Administration (FDA) last January.

“Reports of lung cancers bearing mutations in BRAF have generated considerable interest because these mutations may be associated with increased sensitivity to BRAF tyrosine-kinase inhibiting agents,” Dr. Planchard said in an ESMO press release.

“These findings establish dabrafenib as an effective treatment option for patients with previously treated advanced BRAF V600E non-small cell lung cancer”, concluded Dr. Planchard.

Another study entitled “Neratinib (N) with or without temsirolimus (TEM) in patients (pts) with non-small cell lung cancer (NSCLC) carrying HER2 somatic mutations: An international randomized phase II study”, presented by Dr. Benjamin Besse, head of the thoracic cancer unit at Gustave Roussy, Paris, France,  showed data suggesting that the inhibition of HER2 is important for HER2+ NSCLC.

This study was a randomised, two-stage study, including 27 patients with advanced, metastatic non-small cell lung cancer with tumours positive for HER2 somatic mutations, who were treated with oral neratinib alone or in combination with intravenous temsirolimus.

Preliminary results showed that the combination of neratinib and temsirolimus had a 21% overall response rate in 14 patients, with a median progression-free survival of 4 months.

“HER2 mutated non-small cell lung cancer patients are a small subset of non-small cell lung cancer patients—around 1-2%—but it seems important to inhibit HER2 for these patients. Neratinib inhibits the HER2 receptor while temsirolimus inhibits mTOR, a protein that belongs to the signalling cascade of HER2”,  Dr. Besse explained in the ESMO press release.

“HER2 mutated non-small cell lung cancer represents a very small number of patients, but it reflects the new face of NSCLC –it is not a single homogeneous disease, but a lot of different molecularly defined subsets of patients with potential ‘drugable targets’, for which specific strategies should be addressed.” Dr. Besse concluded.

Dr. Fiona Blackhall, medical oncologist and senior lecturer at The Christie NHS Foundation Trust, and Manchester University, Manchester, United Kingdom, commented on the two studies: “Diagnosis of the molecular subtype of lung cancer is central to identification of more effective treatments”.

“Studies of targeted approaches in molecularly defined subsets of non-small cell lung cancer are consistently yielding better response rates and survivals than historical studies conducted in non molecularly selected populations. The principles of precision medicine are proven for non-small cell lung cancer, and now efforts must intensify to ensure equitable access to molecular diagnostics for patients with this disease,” Dr. Blackhall concluded.

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