Talimogene laherparepvec extended OS in metastatic melanoma

Patients with metastatic melanoma treated with talimogene laherparepvec experienced longer survival than those treated with granulocyte-macrophage colony-stimulating factor, according to interim OS results of an open-label phase 3 study.

The OPTiM trial included 436 patients (median age, 63 years; 57% men) with unresected stage IIIB, IIIC or IV melanoma.

Howard L. Kaufman, MD, professor and director of the section of surgical oncology in the department of general surgery at Rush University Medical Center in Chicago, and colleagues randomly assigned 295 patients to talimogene laherparepvec [T-VEC (Amgen)] intralesionally biweekly. The other 141 patients received granulocyte macrophage colony–stimulating factor (GM-CSF) subcutaneously for the first 14 days of each 28-day cycle.

Patients treated with T-VEC had a median overall survival of 23.3 months, compared with 19 months for those treated with GM-CSF (HR=0.79; 95% CI, 0.61-1.02). There were pronounced survival rate differences in a subset of patients with stage IIIB, IIIC or IV M1a disease (HR=0.56; 95% CI, 0.38-0.81) and those who received first-line treatment with T-VEC (HR=0.49; 95% CI, 0.33-0.74), with each cohort comprising about 50% of the patient population.

“A favorable trend in overall survival was observed in patients who received talimogene laherparepvec and the trend was pronounced in patients with stage III and IV M1a disease, where an important clinical need exists for patients whose disease has not yet spread to distant organs,” Kaufman said in a press release. “I look forward to seeing the final results next year.”

T-VEC is an oncolytic immunotherapy derived from herpes simplex virus type-1. Upon injection directly into tumor tissue, T-VEC selectively infects and replicates in tumor cells. The virus replication leads to tumor cell lysis and exposure of tumor-specific antigens to the immune system, resulting in a local and systemic immune activation and an immune-mediated destruction of tumor cells throughout the body.

T-VEC also is engineered to produce GM-CSF to enhance the local and systemic antitumor immune response.

The interim OS results complement durable response data reported earlier this year, said Sean E. Harper, MD, executive vice president of research and development at Amgen.

Findings presented at the ASCO Annual Meeting in June showed higher objective response rates (26% vs. 6%) and complete response rates (11% vs. 1%) among patients assigned to T-VEC. T-VEC also was associated with a statistically significant improvement in durable response rate (16% vs. 2%). Patients with earlier-stage disease had the highest rates of durable response.

“These endpoints appear to correlate with each other in terms of where the most benefit is being seen in this trial,” Harper said. “We look forward to the mature overall survival data expected in the first half of next year.”

Adverse events included fatigue, chills and pyrexia. Serious adverse events included disease progression in both treatment groups, and cellulitis and pyrexia in the T-VEC cohort. Researchers reported serious adverse events in 26% of patients treated with T-VEC and 13% of patients treated with GM-CSF.

For more information:

Kaufman HL. Interim OS subset analyses in OPTiM, a randomized phase 3 trial of intralesional talimogene laherparepvec vs. subcutaneous granulocyte macrophage-colony stimulating factor in stage IIIB-IV melanoma. Presented at: Society for Melanoma Research; Nov. 17-20, 2013; Philadelphia.