Villejuif, le 6 juin 2016
Lung cancer: efficacy of targeted therapies combination
Two oral communications on targeted therapies for lung cancer are being presented at the 52nd ASCO annual meeting. One of these was led by Dr. David Planchard, Pneumo-Oncologist in the Gustave Roussy Department of Medical Oncology. It demonstrates that a combination of the two targeted therapies, trametinib and dabrafenib, is effective in overcoming resistance in lung cancer with the BRAFV600E mutation.
The second, the ULTIMATE study, was led jointly by Dr. Benjamin Besse, Head of the Thoracic Pathology Committee in the Gustave Roussy Department of Medical Oncology, and Alexis Cortot (Pneumo-Oncologist at the Lille CHRU [Regional University Hospital Centre]). This compares the activity of docetaxel chemotherapy with a combination of paclitaxel chemotherapy and bevacizumab, an antiangiogenic targeted therapy. The dual therapy was superior to chemotherapy alone.
Combining two targeted therapies to overcome resistance
Beyond first-line therapy, a combination of two targeted therapies, dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor), seems to be very effective in non-small cell lung cancer with the BRAFV600E mutation (which is currently tested for routinely in INCa [National Institute for Cancer] molecular biology laboratories).
This was an international phase II trial in 57 patients led by Dr David Planchard. It was the first trial using this combination of drugs in lung cancer. The objective response rate was 63% and the median disease progression-free period was 9.7 months with a median response duration of 9 months. In addition, safety was good and the main side effects were easy to manage.
David Planchard, in a study presented at ASCO in 2015 and published in Lancet Oncology, had previously shown that dabrafenib (a BRAF inhibitor) given as monotherapy produced an overall response rate of 33% in patients with lung cancer carrying the BRAF V600E mutation. The combination of two targeted therapies in this latest study increases the clinical benefit markedly and may in the near future represent a new standard therapy for these patients.
> Read the abstract: An open-label phase II trial of dabrafenib (D) in combination with trametinib (T) in patients (pts) with previously treated BRAF V600E– mutant advanced non-small cell lung cancer (NSCLC; BRF113928).
ULTIMATE: ta rgeted therapy and chemotherapy versus chemotherapy alone
The randomised phase III clinical trial, ULTIMATE, evaluated the bevacizumab-paclitaxel (wPB) combination versus docetaxel, in second or third-line treatment in patients with advanced, nonsquamous non-small cell lung cancer resistant to first-line therapy. This study, led by Dr. Alexis Cortot, (1st author), and Dr. Benjamin Besse, (last author), showed the wPB combination to be superior to monotherapy.
The principal end-point, median progression-free survival, was 5.4 months for patients given wPB versus 3.9 months for those given docetaxel alone. The hazard ratio was 0.62, representing a 38% decrease in the risk of disease progression. The objective response rates were 22.5% and 5.5% respectively with the haematological side-effect profile being better in the dual therapy group.
The addition of bevacizumab to paclitaxel had been shown to be synergistic and to improve the positive effects of this drug in various cancers. The promising results of the ULTIMATE trial suggest that wPB should be one of the standard treatments for this condition.
> Read the abstract: Weekly paclitaxel plus bevacizumab versus docetaxel as second or third-line treatment in advanced non-squamous non-small cell lung cancer (NSCLC): Results from the phase III study IFCT-1103 ULTIMATE.