A phase II trial of motexafin gadolinium (MGd) in advanced non-small cell lung cancer (NSCLC) patients who had failed platinum-based chemotherapy: Preliminary results of stage 1

Abstract

18001 Background: Motexafin gadolinium (MGd) is a tumor-selective antineoplastic agent that disrupts redox dependent pathways by targeting oxidative stress-related proteins such as thioredoxin reductase (TRX). TRX often is overexpressed in NSCLC and is associated with a poor prognosis. Inhibition of TRX reverses tumor phenotype in lung carcinoma cells in vitro and in vivo. This randomized 2-stage phase II trial investigated tumor response and survival with 2 regimens of single agent MGd for the 2nd line treatment of advanced NSCLC. Methods: Patients with locally advanced or metastatic NSCLC ± brain metastases, ECOG PS 0–1, who had received one prior platinum-based chemotherapy regimen ± kinase inhibitor were randomized to intravenous MGd (10 mg/kg/week - Group A) or MGd (15 mg/kg/q 3 weeks - Group B) given in 21 day cycles. The sample size was 30 per arm in stage 1, and 24 per arm in stage 2. Response was evaluated by RECIST every 6 weeks. Results: 51 evaluable patients, median age of 62 years (range 41–85), with locally advanced (14%) or metastatic (86%) adenocarcinoma (47%), squamous cell carcinoma (14%), large cell carcinoma (10%), bronchoalveolar carcinoma (2%) or other NSCLC (27%) were randomized to group A (N=22) or group B (N=29). 37% had not responded to first line chemotherapy. MGd treatment was well tolerated, with 1–12 cycles (median 2, mean 3) administered. The most common grade 3+ adverse events were hypophosphatemia (15.7%), fatigue (13.7%), dyspnea (9.8%), hypoxia (7.8%), and finger blisters (5.9%). 48 patients were evaluable for response, with a confirmed response rate of 4.2% (2 PR). Median time to progression was 7 weeks in each group, with 26% and 15% free from progression at 4 and 6 months, respectively. Median survival of 51 evaluable patients was 10.2 months (95% CI: 6.7 months - not reached), 9.2 months for group A and not reached at > 1 year for group B. Conclusions: MGd appears active as a single agent for second line treatment of NSCLC patients with advanced or metastatic NSCLC who have failed prior platinum-based chemotherapy, with a modest response rate and promising survival. The trial has met the criteria for continuation into stage 2 for each treatment group. No significant financial relationships to disclose.