Primary and secondary endpoints failure for NSCLC drug

Two pivotal Phase III studies, initiated by San Diego-based Ligand Pharmaceuticals, using its Targretin (bexarotene) capsules in front-line combination therapy with standard chemotherapy to treat advanced non-small cell lung cancer (NSCLC), failed to meet their endpoints of improved overall survival and projected two-year survival.

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 SPIRIT I, patients were randomised to two arms, receiving either cisplatin/vinorelbine chemotherapy alone or in combination with Targretin capsules. SPIRIT II enrolled patients to two arms receiving either carboplatin/paclitaxel alone or in combination with Targretin capsules.

For both studies, the primary endpoint was overall survival and the secondary endpoint was Kaplan-Meier projected two-year survival. No statistically significant differences in primary or secondary endpoints in the intent to treat population were seen in either trial.

'We are very disappointed in the lack of survival advantage of Targretin/dual chemotherapy triple therapy in first-line NSCLC patients, particularly in view of the consistent positive trends seen in several phase I/II studies and in the preclinical data that provided strong mechanistic support for a potentially beneficial Targretin/chemotherapy combination,' said Dr Andres Negro-Vilar, Ligand's executive vice president for research and development and chief scientific officer. 'We know that several other targeted therapies combined with chemotherapy have also fallen short of a survival advantage in a first-line setting while in some cases proving efficacious in second- and third-line treatment. We believe SPIRIT I and II provided robust data to evaluate the value of adding Targretin to combo chemotherapy in the front-line setting and based upon those results now plan to continue to evaluate the potential of Targretin to provide benefit for second- and third-line patients.'