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Injecting an engineered herpes virus into melanoma lesions produced lasting shrinkage in about one patient in six, compared with one in fifty on the control drug, but it did not clearly help people live longer.
Open-label phase 3 trial randomising 436 patients with unresectable stage IIIB to IV melanoma 2:1 to talimogene laherparepvec injected into lesions or subcutaneous granulocyte-macrophage colony-stimulating factor. The primary endpoint was durable response rate, defined as an objective response lasting continuously for at least six months, judged by independent assessment.
Durable response rate was 16.3 per cent with talimogene laherparepvec against 2.1 per cent with the control, odds ratio 8.9. Overall response rate was 26.4 per cent against 5.7 per cent. Median overall survival was 23.3 months against 18.9 months, hazard ratio 0.79, p = 0.051, which did not meet significance. Benefit concentrated in stage IIIB, IIIC and IVM1a disease and in patients who had not been treated before. The commonest adverse events were fatigue, chills and fever; the only grade 3 or 4 event in at least 2 per cent of treated patients was cellulitis.
The gap between the response result and the survival result is the single most important fact about this field. It is a licensing trial built on a response endpoint whose survival comparison did not reach significance, against a comparator that is not a modern melanoma treatment.
This is the approval that created the class, and it is also the clearest example of how the class is oversold. A durable response rate eight times the comparator is a real local effect on injectable lesions. The survival comparison did not reach significance, and the comparator was granulocyte-macrophage colony-stimulating factor rather than a checkpoint inhibitor, which by 2015 was already the standard. A reader told that a virus improves survival in melanoma is being told something this trial did not show.
Shares Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma, Talimogene laherparepvec, Oncolytic viruses, Melanoma.
Shares Howard L. Kaufman, Talimogene laherparepvec, Oncolytic viruses.
Shares Talimogene laherparepvec, Amgen, Melanoma.
Shares Talimogene laherparepvec, Amgen, Melanoma.
Shares Talimogene laherparepvec, Amgen, Melanoma.
Shares Oncolytic viruses, Advanced melanoma (unresectable stage III and stage IV), Journal of Clinical Oncology, Melanoma.
Shares Talimogene laherparepvec, Oncolytic viruses, Melanoma.
Shares Amgen, Advanced melanoma (unresectable stage III and stage IV), Melanoma.