Background: Preliminary results indicated that bortezomib (B) (Velcade*) as a single agent may have activity in pretreated NSCLC patients with similar or lesser toxicity compared to chemotherapy. This phase II study was initiated to determine the efficacy of single-agent B in chemonaïve patients with advanced NSCLC. An early tumor assessment (after 6 weeks of therapy) was performed to allow for rapid and appropriate management of non-responding patients.
Methods: Patients received B (1.5 mg/m2) twice a week for 2 consecutive weeks (days 1, 4, 8, and 11) followed by a 10-day rest period. The primary endpoint was non-progression rate (NPR) after 6 weeks of treatment. Secondary endpoints included response rate, progression-free survival (PFS), overall survival (OS), and safety. Exploratory analyses included FDG-PET response at 6 weeks and circulating tumors cell (CTC) assessment at day 1 of each cycle in a subset of patients.
Results: 18 patients were enrolled from 06/06 to 02/07 from 3 French institutions.
Demographics: male/female 15/3; median age 66 (54-79); PS 0/1/2, 3/12/3; pathology: adenocarcinoma 11, squamous cell carcinoma 5, large-cell carcinoma 2; smoking status never/former/current 1/10/7; stage IIIB/IV 2/16. Seventeen patients received B and 16 were assessable (1 early withdrawal and 1 progression at D26). The most frequent toxicity was fatigue (17 patients). Twelve patients (71%) had at least one grade 3 toxicity: 4 haematological, 1 infection, 5 gastro-intestinal toxicity, 9 fatigue, 1 neuropathy. The non-progression rate was 59% [33-82%] at 6 weeks (10/17 patients). No objective response was seen. With a median follow-up of 12.3 months, the median PFS and OS were 2.4 and 9.8 months respectively. Eleven deaths occurred. No PET response was observed, and CTC were detected only in 1 out of 8 patients evaluated.
Conclusions: Although according to the protocol rules the trial should not be stopped, the lack of any objective response either by CT-scan or PET-CT, along with substantial toxicity, did not argue in favor of the current strategy of B as a single agent in the front-line setting of NSCLC.
Trial registration: ClinicalTrials.gov NCT00508625.
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