Addition of Linifanib to Carboplatin-Paclitaxel Increases Progression-Free Survival and Toxicity in Advanced Nonsquamous NSCLC

In a phase II trial reported in the Journal of Clinical Oncology doctors reported that the addition of linifanib to carboplatin-paclitaxel chemotherapy the outcomes in patients with advanced nonsquamous non–small cell lung cancer (NSCLC). However the addition of linifanib did result in greater side effects from treatment.

Lung cancer remains the leading cause of cancer-related deaths worldwide. In the United States, NSCLC accounts for 75–80% of all lung cancers. Although progress has been made in recent years the majority of patients with advanced stage lung cancer still die from their disease. New treatments are sorely needed.  Investigators recently reported that the use of linifanib in NSCLC appears promising.

Linifanib is an orally active multi-targeted receptor tyrosine kinase inhibitor being developed for the treatment of various cancers. The compound is designed to inhibit vascular endothelial growth factor and platelet-derived growth factor receptors.

In the current study, 138 patients with stage IIIB/IV nonsquamous NSCLC were treated with a regimen of carboplatin and paclitaxel chemotherapy every 3 weeks with or without linifanib and directly compared.

The average duration of survival without cancer progression was improved from 5.4 months to 8.3 months with the addition of linifanib and overall survival was increased from 11.3 to 13 months.  Side effects that were more common with linifanib treatment included diarrhea, anemia, hypertension, weight loss and toxicity to the skin.  Thrombocytopenia or a low platelet blood count was the most common reason for treatment interruption or dose reduction of carboplatin and paclitaxel.

The addition of linifanib to chemotherapy significantly improved progression-free survival with a modest trend for improved survival and additional studies are ongoing to determine the optimal role of linifanib in the management of NSCLC.

Reference: Ramalingam S, Shtivelband M, Soo R, et al. Randomized Phase II Study of Carboplatin and Paclitaxel With Either Linifanib or Placebo for Advanced Nonsquamous Non–Small-Cell Lung Cancer. J Clin Oncol. Published online before print January 5, 2015, doi: 10.1200/JCO.2014.55.7173

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