T-VEC extends OS in patients with unresected stage III/IV melanoma

Issue: May 10, 2015

NEW YORK — Patients with unresected stage IIIb, stage IIIc or stage IV melanoma treated with talimogene laherparepvec demonstrated a durable OS advantage compared with those who received granulocyte-macrophage colony–stimulating factor, according to study results presented at the HemOnc Today Melanoma and Cutaneous Malignancies meeting.

Talimogene laherparepvec (T-VEC, Amgen) is a systemically active 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.

Robert H.I. Andtbacka

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

Robert H.I. Andtbacka, MD, CM, associate professor in the division of surgical oncology at the University of Utah School of Medicine, a surgeon and investigator with Intermountain Healthcare and Huntsman Cancer Institute, and a HemOnc Today Editorial Board member, and colleagues conducted the randomized phase 3 OPTiM trial to compare T-VEC with GM-CSF in patients with unresectable stage IIIb, stage IIIc or stage IV melanoma.

All patients were aged 18 years or older and had injectable cutaneous, subcutaneous or nodal lesions. All patients had up to three visceral lesions but none were larger than 3 cm.

The intention-to-treat analysis included 496 patients (median age, 63 years; 57% men). Of these, 295 (68%) received intralesional T-VEC at an initial dose of ≤4 mL x 10⁶ pfu/mL. After 3 weeks, the dose was changed to ≤4 mL x 10⁸ pfu/mL every 2 weeks.

The other 141 (32%) patients received subcutaneous GM-CSF administered in doses of 125 µg/m² daily for 14 days every 4 weeks.

Andtbacka presented results of the final OS analysis, performed at 3 years from the last randomization. Median follow-up was 49 months (range, 37-63).

Results showed patients assigned T-VEC experienced significantly longer median OS (23.3 months vs. 18.9 months; HR = 0.79; 95% CI, 0.62-1). More than one-third (38.9%) of patients assigned T-VEC survived at least 3 years.

Researchers determined the survival advantage associated with T-VEC was most apparent in patients with M1a melanoma (HR = 0.56; 95% CI, 0.4-0.79) and those with treatment-naive disease (HR = 0.5; 95% CI, 0.35-0.72).

The fact the OS advantage with T-VEC persisted throughout extended follow-up suggests the agent is a potential new treatment for patients with regionally and distantly metastatic melanoma, Andtbacka and colleagues concluded. – by Cameron Kelsall

Reference:

Andtbacka RHI, et al. Final analysis of overall survival (OS) from OPTiM, a randomized phase 3 trial of talimogene laherparepvec (T-VEC) versus GM-CSF to treat patients with unresected stage IIIB/C/IV melanoma. Presented at: HemOnc Today Melanoma and Cutaneous Malignancies; April 10-11, 2015; New York.

Disclosure: Andtbacka reports research funding from Amgen, Takara and Viralytics, and a consultant role with Amgen. See the full study for a list of all other researchers’ relevant financial disclosures.