Mixed Results Reported for Talimogene Laherparepvec in Patients With Metastatic Melanoma
Treatment shrinks tumors but doesn’t improve survival in phase III trial
Mixed results have been reported from the primary overall survival (OS) analysis of a phase III trial in melanoma that evaluated the efficacy and safety of talimogene laherparepvec (Amgen) for the treatment of unresected stage IIIB, IIIC, or IV melanoma compared with treatment with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF).
The results showed that, while the primary endpoint of a durable response rate was met, the secondary endpoint of OS was not met, although there was a strong trend in favor of talimogene laherparepvec (P = 0.051). The estimated OS hazard ratio and improvement in median OS were similar to what was previously reported at the interim OS analysis.
The global, randomized, open-label phase III trial enrolled patients with unresected stage IIIB, IIIC, or IV melanoma. The patients were randomly assigned to receive either talimogene laherparepvec every 2 weeks through direct tumor injection or GM-CSF subcutaneously for the first 14 days of each 28-day cycle for up to 18 months.
The most frequent adverse events observed in this trial were fatigue, chills, and pyrexia. The most common serious adverse events included disease progression, cellulitis, and pyrexia.
Talimogene laherparepvec is an investigational oncolytic immunotherapy designed to selectively replicate in tumors (but not in normal tissue) and to initiate an immune response to target cancer cells that have metastasized. The treatment was designed to work in two complementary ways. First, it is injected directly into tumors, where it replicates inside the tumor’s cells, causing cell lysis. The rupture of the cancer cells then releases tumor-derived antigens, along with GM-CSF, that can stimulate a systemwide immune response in which white blood cells are able to seek out and target cancer that has spread throughout the body.
Melanoma is characterized by the uncontrolled growth of melanocytes. It is the most aggressive and serious form of skin cancer. Currently, 132,000 melanoma cases occur globally each year. In the U.S., while melanoma accounts for less than 5% of skin cancer cases, it causes the most skin cancer deaths. The number of new cases of melanoma in the U.S. has been increasing for the last 30 years.
Source: Amgen; April 4, 2014.