Ligand Pharmaceuticals has reported results of two pivotal Phase III studies of Targretin (bexarotene) capsules in front-line combination therapy with standard chemotherapy to treat advanced non-small cell lung cancer (NSCLC).

The two pivotal Phase III studies did not meet their endpoints of improved overall survival and projected two-year survival. Those results were consistent between both trials despite different geographical study sites and chemotherapy regimens on the intent to treat analysis. In both trials, additional subset analysis completed after the initial intent to treat results were analyzed reveals a significant correlation between high-grade (Grade 3/4) hypertriglyceridemia and increased survival, potentially identifying a large subgroup patient population that may receive significant survival benefit of added Targretin treatment in first line therapy.

The studies were designed to evaluate whether adding Targretin to front-line cisplatin/vinorelbine or carboplatin/paclitaxel chemotherapy extends the survival of patients with advanced (Stage IIIB with pleural effusion or Stage IV) NSCLC. In the SPIRIT I trial, 623 patients were equally randomized to two arms, stratified by sex and disease stage, receiving cisplatin/vinorelbine chemotherapy alone or in combination with Targretin capsules. SPIRIT II enrolled 612 patients equally randomized and stratified to two arms receiving carboplatin/paclitaxel alone or in combination with Targretin capsules.