In a nutshell
The objective of this study was to determine whether addition of linifanib to a combination of carboplatin (Paraplatin) and paclitaxel (Taxol) could benefit advanced nonsquamous non-small cell lung cancer (NSCLC) patients.
Some background
Nonsquamous NSCLC is a type of lung cancer where the cancer starts in cells other than squamous (flat cells that line the inside of the lungs). Combination chemotherapy with carboplatin and paclitaxel has shown average improvement in overall survival with advanced NSCLC patients. Linifanib is an orally active drug that acts by stopping the function of key proteins involved in NSCLC. In previously reported preclinical studies, carboplatin and paclitaxel were shown to be more effective in the presence of linifanib in NSCLC.
Methods & findings
In this phase II study, 138 patients with stage IIIB or IV nonsquamous NSCLC were included. Patients were randomly assigned to three groups to receive placebo (a substance that has no therapeutic effect, used for control in testing new drugs), linifanib 7.5 mg or linifanib 12.5 mg. In addition, patients in each group received a combination of carboplatin and paclitaxel. The effect of linifanib was also evaluated in patients who had the NSCLC specific biomarker CEA/CYFRA in their blood samples. Biomarkers are naturally occurring body substances (often proteins) associated with a disease and used for predicting the progression of a disease.
The average progression-free survival (time following treatment before the disease progresses) was higher in linifanib 7.5 mg group (252 days compared with 221 days with linifanib 12.5 mg), with 49% reduced risk or death. Men in this group had 66% reduced risk or death compared to 7% for women. Duration of overall survival was between 343 and 396 days for all three groups. A significant improvement in progression-free survival was noted with either dose of linifanib in patients with CEA/CYFRA biomarker profile.
Some of the severe side effects associated with either dose of linifanib were diarrhea, anemia, high blood pressure, and impairment of voice (dysphonia).
The bottom line
In summary, progression-free survival of advanced nonsquamous NSCLC patients was significantly improved when linifanib 7.5 mg was added to combination chemotherapy of carboplatin and paclitaxel.
The fine print
Both doses of linifanib (7.5 and 12.5 mg) led to increased toxicity.
What’s next?
Consult with your physician about the use of linifanib with carboplatin–paclitaxel chemotherapy.
Published By :
Journal of clinical oncology
Date :
Jan 05, 2015
