In the JournalsPerspective

Higher response rate seen with T-VEC in advanced melanoma

Patients with unresected stage IIIB to IV melanoma who were treated with talimogene laherparepvec experienced a higher durable response rate than patients treated with granulocyte macrophage colony-stimulating factor, according to recently published results of a phase 3 trial.

Talimogene laherparepvec (T-VEC; Amgen) is a systemically active oncolytic immunotherapy derived from herpes simplex virus type-1.

Robert H.I. Andtbacka, MD, CM, and colleagues conducted the open-label study between May 2009 and July 2011 at 64 centers in the United States, the United Kingdom, Canada and South Africa. Researchers randomly assigned 436 patients with injectable melanoma that was not surgically resectable in a 2:1 ratio to treatment with intralesional T-VEC (n=295) or subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF; n=141). Fifty-seven percent of patients had stage IIB, IIC or IVM1a disease.

Robert H.I. Andtbacka, MD

Robert H.I. Andtbacka

Durable response rate — objective response lasting continue continuously for ≥ 6 months — per independent assessment was used as primary end point.

The T-VEC treatment cohort experienced significantly higher durable response rate (16.3%; 95% CI, 12.1%-20.5%) compared with the GM-CSF-treated patients (2.1%; 95% CI, 0%-4.5%). Patients who received T-VEC also higher overall response rate (26.4%; 95% CI, 21.4%-31.5%) vs. the GM-CSF cohort (5.7%; 95% CI, 1.9% to 9.5%).

Patients treated with T-VEC had a median overall survival of 23.3 months (95% CI, 19.5 to 29.6 months) compared with 18.9 months (95% CI, 16 to 23.7 months) with GM-CSF (HR = 0.79, 95% CI, 0.62-1). Patients with stage IIIB, IIC or IVM1a disease and patients with treatment-naive disease experienced the most pronounced T-VEC efficacy.

The T-VEC patients experienced more adverse events compared with the GM-CSF cohort (49% vs. 9%), with pyrexia, injection-site pain, nausea, influenza-like illness and fatigue, the most commonly reported adverse events for the T-VEC cohort. Cellulitis was the only grade 3 or 4 adverse event that occurred in at least 2% of the T-VEC treatment cohort (n=6). There were no treatment-related fatal adverse events reported.

“T-VEC treatment resulted in long-lasting [complete responses], suggesting T-VEC could delay or prevent relapses or preclude progression to later stages of disease,” the researchers concluded. — by Bruce Thiel

Disclosure: Andtbacka reports honoraria from Amgen and Novartis, consulting or advisory roles with Amgen and Merck, speakers’ bureau role with Novartis and research funding to his institution from Amgen, Takeda Pharmaceuticals and Viralytics. Please see the study for a full list of the other researchers’ relevant financial disclosures.

 

Patients with unresected stage IIIB to IV melanoma who were treated with talimogene laherparepvec experienced a higher durable response rate than patients treated with granulocyte macrophage colony-stimulating factor, according to recently published results of a phase 3 trial.

Talimogene laherparepvec (T-VEC; Amgen) is a systemically active oncolytic immunotherapy derived from herpes simplex virus type-1.

Robert H.I. Andtbacka, MD, CM, and colleagues conducted the open-label study between May 2009 and July 2011 at 64 centers in the United States, the United Kingdom, Canada and South Africa. Researchers randomly assigned 436 patients with injectable melanoma that was not surgically resectable in a 2:1 ratio to treatment with intralesional T-VEC (n=295) or subcutaneous granulocyte macrophage colony-stimulating factor (GM-CSF; n=141). Fifty-seven percent of patients had stage IIB, IIC or IVM1a disease.

Robert H.I. Andtbacka, MD

Robert H.I. Andtbacka

Durable response rate — objective response lasting continue continuously for ≥ 6 months — per independent assessment was used as primary end point.

The T-VEC treatment cohort experienced significantly higher durable response rate (16.3%; 95% CI, 12.1%-20.5%) compared with the GM-CSF-treated patients (2.1%; 95% CI, 0%-4.5%). Patients who received T-VEC also higher overall response rate (26.4%; 95% CI, 21.4%-31.5%) vs. the GM-CSF cohort (5.7%; 95% CI, 1.9% to 9.5%).

Patients treated with T-VEC had a median overall survival of 23.3 months (95% CI, 19.5 to 29.6 months) compared with 18.9 months (95% CI, 16 to 23.7 months) with GM-CSF (HR = 0.79, 95% CI, 0.62-1). Patients with stage IIIB, IIC or IVM1a disease and patients with treatment-naive disease experienced the most pronounced T-VEC efficacy.

The T-VEC patients experienced more adverse events compared with the GM-CSF cohort (49% vs. 9%), with pyrexia, injection-site pain, nausea, influenza-like illness and fatigue, the most commonly reported adverse events for the T-VEC cohort. Cellulitis was the only grade 3 or 4 adverse event that occurred in at least 2% of the T-VEC treatment cohort (n=6). There were no treatment-related fatal adverse events reported.

“T-VEC treatment resulted in long-lasting [complete responses], suggesting T-VEC could delay or prevent relapses or preclude progression to later stages of disease,” the researchers concluded. — by Bruce Thiel

Disclosure: Andtbacka reports honoraria from Amgen and Novartis, consulting or advisory roles with Amgen and Merck, speakers’ bureau role with Novartis and research funding to his institution from Amgen, Takeda Pharmaceuticals and Viralytics. Please see the study for a full list of the other researchers’ relevant financial disclosures.

 

    Perspective
    Andrew F. Alexis

    Andrew F. Alexis

    Talimogene laherparepvec (T-VEC) is a novel therapeutic option for patients with metastatic melanoma that not only selectively targets melanoma cells (via genetically modified herpes simplex 1) but also, enhances systemic antitumor immune responses (by producing granulocyte macrophage colony-stimulating factor).

    It is the first oncolytic immunotherapy to demonstrate efficacy in the treatment of melanoma in a phase III clinical trial. Patients treated with T-VEC had a higher durable response rate (objective continuous response lasting at least 6 months) and longer median overall survival than those in the control group (granulocyte macrophage colony-stimulating factor (GM-CSF). Notably, 11% of patients achieved a complete response, which is very encouraging. While efficacy was demonstrated in all stages of metastatic melanoma, the response was greater in patients with stage IIIB, IIIC, or IVM1a than in those with stage IVM1b disease.

    The results of this study are exciting in that they offer hope to patients with inoperable melanomas – a population with limited effective treatment options and low response rates to currently available therapies.

    • Andrew F. Alexis, MD
    • Chairman Department of Dermatology Mount Sinai St. Luke's and Mount Sinai Roosevelt

    Disclosures: Alexis reports having served as a consultant for Amgen and having received honoraria for such services.