Talimogene Laherparepvec Improves Durable Response Rate in Patients With Advanced Melanoma

Abstract

T-VEC is the first oncolytic immunotherapy to demonstrate therapeutic benefit against melanoma in a phase III clinical trial. T-VEC was well tolerated and resulted in a higher DRR (P < .001) and longer median OS (P = .051), particularly in untreated patients or those with stage IIIB, IIIC, or IVM1a disease. T-VEC represents a novel potential therapy for patients with metastatic melanoma.

Targeted agents and immunotherapies: optimizing outcomes in melanoma

“…For such visible lesions, regression of the injected tumours was reproducibly demonstrated. Unlike with other injectable agents, responses to T-VEC were observed in adjacent uninjected lesions, and occasionally at distant metastases 96,98 .…”

“…OPTiM had eligibility parameters chosen to select for patients with a relatively limited extent of distant metastatic disease; many patients had regionally advanced disease only. Differences in the durable response rates with the use of T-VEC versus GM-CSF were more pronounced in patients with stage IIIB-C (33% versus 0%) or IVM1a disease (16% versus 2%) than in those with stage IVM1b (3% versus 4%) or IVM1c disease (7% versus 3%) 98 . Accordingly, the systemic utility of this approach must be considered in the context of the other available systemic agents associated with higher rates of disease control.…”

“…By this end point, 16.3% of patients treated with T-VEC had a protocol-defined durable response compared with 2.1% with GM-CSF 98 . OPTiM had eligibility parameters chosen to select for patients with a relatively limited extent of distant metastatic disease; many patients had regionally advanced disease only.…”

“…The rate of durable response (lasting ≥6 months, although a patient could initially have disease progression by RECIST criteria) in injected and non-injected lesions was the primary end point of the phase III OPTiM trial 98 , in which T-VEC was compared to subcutaneously administered GM-CSF. By this end point, 16.3% of patients treated with T-VEC had a protocol-defined durable response compared with 2.1% with GM-CSF 98 .…”

Tumour devascularisation as a potential immunotherapeutic strategy

“…Injections of talimogene laherparepvec (T-Vec), a genetically engineered herpes virus, resulted in the regression of treated as well as untreated tumour lesions accompanied by increased intratumoural infiltration by melanoma-specific CD8 + cells and reduced numbers of CD4 + Foxp3 + T regulatory cells. 34 …”