Agent that Targets Heat Shock Protein Shows Activity in Castration-Resistant Prostate Cancer

August 2012 Vol 5, No 5, Special Issue ASCO 2012 Payers' Perspective
Wayne Kuznar

Chicago, IL—OGX-427, a second-generation investigational antisense compound that targets heat shock protein-27 (Hsp-27), is well tolerated, and when combined with prednisone in patients with chemotherapy-naive metastatic castration-resistant pros­tate cancer (CRPC), it reduces disease progression compared with prednisone alone.

In a recent clinical study, more patients who took OGX-427 plus prednisone were without disease progression at 12 weeks and more had declines in levels of prostate-specific antigen (PSA) compared with those taking prednisone alone, reported Kim Chi, MD, medical oncologist and Associate Professor of Medicine at BC Cancer Agency, British Columbia, Canada, and the primary study investigator, at ASCO 2012.

Hsp-27 is a cell-survival protein expressed in many types of cancers. Overexpression of Hsp-27 is thought to be an important factor leading to the development of treatment resistance and is correlated with a poorer prognosis in patients with various tumor types. “It also increases after castration therapy as a stress survival response and is shown to be overexpressed highly in metastatic CRPC tissues,” said Dr Chi.

Of 72 planned patients, 64 have been randomized to the study, and data on 42 patients (22 who received OGX-427 plus prednisone, and 20 who received prednisone alone) are now available at or beyond the 12-week assessment time point.

The median treatment duration is 24 weeks in the OGX-427 plus prednisone arm versus 14 weeks in the prednisone alone arm. Treatment is ongoing in approximately 30% of patients in each arm. Of the 14 patients in the prednisone alone arm who have come off treatment, 13 have done so because of disease progression, said Dr Chi. For this reason, 10 of the 20 patients in the prednisone alone arm crossed over to the OGX-427 plus prednisone arm.

The primary efficacy end point in the study was progression-free survival (PFS) at 12 weeks. Disease progression is based on any of the following parameters: PSA levels, measurable disease, bone lesions, global deterioration, or a requirement for palliative radiation therapy.

In the OGX-427 plus prednisone arm, PFS was 71% at 12 weeks compared with 40% in the prednisone alone arm. A ≥50% decline in PSA was experienced by 50% of patients who were randomized to OGX-427 plus prednisone, versus 20% of patients who were randomized to prednisone alone.

Among the 21 patients with baseline measurable disease, 44% (4 of 9) in the OGX-427 plus prednisone arm had a measurable disease response compared with 0% (0 of 12) in the prednisone alone arm.

There was 1 complete response in the OGX-427 plus prednisone arm. “This has lasted for almost a year, and he still has not progressed,” said Dr Chi.

Circulating tumor cells declined from ≥5/7.5 mL to <5/7.5 mL in 55% of patients receiving OGX-427 plus prednisone compared with 41% in the prednisone alone group.

Adverse events have been predo­m­inantly grade 1 to 2 and related to infusion reactions. “These are predominantly in the first couple of infusions; patients tend to build tolerance, and the reactions are brief and self-limited,” he said. There were 3 grade 4 adverse events reported, including dizziness, pulmonary embolus, and 1 case of hemolytic uremic syndrome.

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Last modified: August 30, 2012
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