FROM JOURNAL OF CLINICAL ONCOLOGY
Treatment with the oncolytic immunotherapy talimogene laherparepvec (T-VEC) resulted in significantly longer rates of durable response and overall response, compared with subcutaneous granulocyte-macrophage colony-stimulating factor (GM-CSF), according to results from the phase III OPTiM trial reported in the Journal of Clinical Oncology.
“To our knowledge, OPTiM is the first randomized, controlled, phase III study evaluating an oncolytic immunotherapy to demonstrate a therapeutic benefit in melanoma,” wrote Dr. Robert Andtbacka, of the Huntsman Cancer Institute, University of Utah, Salt Lake City, and colleagues (J. Clin. Onc. 2015 May 26 [ doi:10.1200/JCO.2014.58.3377 ]).
Patients who received T-VEC vs. subcutaneous GM-CSF had significantly improved rates of durable response, defined as responses lasting 6 months or more, (16.3% vs. 2.1%; P < .001), as well as improved overall response rates (26.4% vs. 5.7% ; P < .001). Complete responses were achieved in 10.8% of the T-VEC arm (32 patients) and < 1% (1 patient) in the GM-CSF arm. Median overall survival was 23.3 months for T-VEC and 18.9 months for GM-CSF (P = .051).
Differences in durable response rates and overall response rates between the T-VEC and GM-CSF arms were greater among patients with stage IIIb or IIIC (33% vs. 0%) and IVM1a disease (16% vs. 2%) than in patients with stage IVM1b (3% vs. 4%) or IVM1c disease (7% vs. 3%). This may be because of insufficient time for the immunotherapy to benefit patients with visceral disease, or because injection of T-VEC into dermal, subcutaneous, and nodal metastases may activate an immune response that preferentially targets metastases in similar anatomic sites.
Among patients in the T-VEC arm who achieved a response, 54% had disease progression prior to response. This pseudoprogression is consistent with other immunotherapies and illustrates the importance of continuing treatment in stable patients despite increasing lesions, the investigators noted.
Based on a modified herpes simplex virus type 1, T-VEC is an oncolytic virus designed to replicate in and lyse tumor cells while promoting an antitumor immune response.
Adverse events more frequently observed in the T-VEC group were flu-like symptoms, including chills, pyrexia, nausea, and fatigue. Incidence of grade 3 or 4 adverse events was 11% for T-VEC and 5% for GM-CSF. The tolerable safety profile of T-VEC is an important factor in considering combined immunotherapy approaches, wrote Dr. Robert Andtbacka and associates.
“The evidence of local and systemic immune responses with T-VEC supports combinations with other immunotherapies as a rational approach. A phase 1b/2 study of T-VEC and ipilimumab is evaluating the safety and efficacy of this combination,” they wrote.
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