Velcade® Moderately Active in Non-Small Cell Lung Cancer

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Cancer News Article

Velcade® Moderately Active in Non-Small Cell Lung Cancer

A multi-center phase II randomized trial has determined that Velcade (bortezomib) has significant activity as a single agent or in combination with Taxotere® (docetaxel) in patients with non-small cell lung cancer (NSCLC) who have failed at least one prior regimen.[1] A SWOG trial concluded that Velcade alone had insufficient activity as a single agent in platinum treated patients and suggested other drugs be added.[2] The results of these two studies were presented May 13-17 at the 2005 annual meeting of the American Society of Clinical Oncology in Orlando, Florida.

Velcade is the first in a new class of anticancer agents known as proteasome inhibitors. Velcade is approved for the treatment of refractory multiple myeloma and is being evaluated for treatment of a variety of hematologic malignancies and solid tumors. Single agent activity of Velcade in NSCLC has previously been reported in a phase II trial presented at ASCO 2004.[3]

In the first trial, Velcade was evaluated for the treatment of patients with advanced NSCLC in a randomized phase II multi-center study. Patients (n=155) who progressed following first line chemotherapy for advanced NSCLC were randomly allocated to treatment with Velcade alone or in combination with Taxotere. The response rate to Velcade alone was 8% vs. 9% for the combination group. Disease stabilization occurred in 21% of patients receiving Velcade alone and 45% in patients receiving Velcade plus Taxotere. The time to progression curves favored the combination arm (1.5 months vs. 4 months). More than 30% of the patients were alive beyond 1 year in both arms of the study. Both regimens were tolerated well, though the incidence of neutropenia was higher in the combination arm.

In the SWOG trial, patients were categorized as platinum sensitive if they progressed more than 90 days after receiving platinum therapy and were deemed platinum refractory if they progressed in less than 90 days. They treated a total of 60 patients and 57 were evaluable for response. They only observed one partial response (5%) in 28 platinum refractory patients and no responses were observed in the 29 platinum sensitive patients. These researchers plan to study the combination of Velcade and topotecan.

Comments: These studies provide the rationale for continued evaluation of Velcade but probably not as a single agent. Clinical trials are underway to evaluate Velcade in combination with standard chemotherapy regimens for front-line and second-line treatment of advanced NSCLC.

References

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[1]Fanucchi MP, Fossella F, Fidias P, et al. Bortezomib with or without docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC): a phase 2 study. Journal of Clinical Oncology. 2005;23:629.

[2]The proteasome inhibitor PS-341 (Bortezomib) in platinum (plat)-treated extensive stage small cell lung cancer (E-SCLC): A SWOG (0327) phase II trial. Journal of Clinical Oncology 2005;23:629, abstract 7047.

[3]Stevenson JP, Nho CW, Johnson SW, et al. Effects of bortezomib (PS-341) on NF-KappaB activation in peripheral blood mononuclear cells (PBMCs) of advanced non-small cell lung cancer (NSCLC) patients: a phase II/pharmacodynamic trial. Journal of Clinical Oncology. 2004;Abstract #7145.