Multicenter, prospective, randomized, phase-II trial of sequential and concurrent oral bexarotene in combination with chemotherapy, in previously untreated patients with advanced NSCLC

Abstract

7353 Background: Recent Phase III trials have failed to show significant differences in survival for patients with Stage IIIB/IV NSCLC treated with various platinum-based chemotherapy regimens. New effective therapies are still needed. Bexarotene (Targretin), a synthetic retinoid analogue approved for patients with cutaneous T-cell lymphoma, binds preferentially to the rexinoid receptor (RXR), potentially providing therapeutic benefits in RXR-expressing tumors. Phase I-II studies of bexarotene in advanced NSCLC have shown promising activity. Methods: Chemotherapy-naïve patients with Stage IV and IIIB with pleural effusion, and ECOG performance status (PS) 0–2, were enrolled on study and treated with carboplatin IV AUC-6 Day 1 and paclitaxel IV 100 mg/m2 Days 1, 8 and 15, every 28 days for up to 4 cycles. Patients were randomized to receive bexarotene orally 400 mg/m2/day either concurrently with chemotherapy from Day 1 or sequentially at the completion of the chemotherapy. Patients were started an antilipid agent 7 days prior to bexarotene therapy. Results: 16 patients (median age 67 years) have been enrolled thus far, 9 of whom have completed the planned 4 cycles of chemotherapy (5 in the sequential and 4 in the concurrent arm). Three patients remain on active therapy and 13 patients are off trial; 6 due to progressive disease, 3 for deteriorating PS, 3 for bexarotene-associated adverse events (AE) and 1 withdrew. Overall, AE were reported in 48% of patients in the sequential arm vs. 51% in the concurrent arm. The incidence of Grade 3–4 AE, regardless of the treatment arm or phase, was < 5%. There were no cases of pancreatitis and no treatment-associated deaths. Conclusions: Our data indicate no detrimental effect of adding bexarotene to weekly carboplatin/paclitaxel. Updated data will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Pharmaceuticals