{"entity":{"id":"paper-andtbacka-optim-talimogene-jco-2015","kind":"paper","name":"OPTiM: the trial that made talimogene laherparepvec the first approved oncolytic virus","aka":[],"tldr":"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.","summary":"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.\n\nDurable 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.\n\nThe 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.","asOf":"2026-09-25","links":[{"label":"JCO 2015","url":"https://doi.org/10.1200/JCO.2014.58.3377"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26014293/"}],"tags":[],"related":["paper-chesney-j-clin-oncol"],"cancers":["melanoma","advanced-melanoma"],"sections":["immunotherapy"],"technologies":["oncolytic-virus"],"targets":[],"drugs":["talimogene-laherparepvec"],"companies":["amgen"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["howard-kaufman"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2015,"doi":"10.1200/JCO.2014.58.3377","pmid":"26014293","authors":"Andtbacka RH, Kaufman HL, Collichio F, et al.","paperType":"rct","findings":["Durable response rate 16.3 per cent (95% CI 12.1 to 20.5) with talimogene laherparepvec versus 2.1 per cent (95% CI 0 to 4.5) with granulocyte-macrophage colony-stimulating factor; odds ratio 8.9, p < 0.001.","Overall response rate 26.4 per cent versus 5.7 per cent.","Median overall survival 23.3 months versus 18.9 months; hazard ratio 0.79 (95% CI 0.62 to 1.00), p = 0.051, not statistically significant.","Effect was largest in stage IIIB, IIIC and IVM1a disease and in treatment-naive patients.","Cellulitis was the only grade 3 or 4 adverse event occurring in at least 2 per cent of treated patients, at 2.1 per cent; no fatal treatment-related events."],"whatItMeans":"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.","caveats":["The comparator arm received granulocyte-macrophage colony-stimulating factor, which is not a standard melanoma treatment; the trial predates the routine use of anti-PD-1 therapy.","Overall survival did not reach statistical significance (p = 0.051).","Open-label, and response assessment in injected lesions is hard to blind.","Requires lesions that can be injected, which restricts use to accessible skin, subcutaneous and nodal disease."],"changedPractice":true,"participants":436},"route":"/key-papers/paper-andtbacka-optim-talimogene-jco-2015/","neighbours":{"paper":[{"id":"paper-chesney-j-clin-oncol","kind":"paper","name":"Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma","route":"/key-papers/paper-chesney-j-clin-oncol/"}],"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"section":[{"id":"immunotherapy","kind":"section","name":"Immunotherapy","route":"/fronts/immunotherapy/"}],"technology":[{"id":"oncolytic-virus","kind":"technology","name":"Oncolytic viruses","route":"/technologies/oncolytic-virus/"}],"drug":[{"id":"talimogene-laherparepvec","kind":"drug","name":"Talimogene laherparepvec","route":"/drugs/talimogene-laherparepvec/"}],"company":[{"id":"amgen","kind":"company","name":"Amgen","route":"/companies/amgen/"}],"person":[{"id":"howard-kaufman","kind":"person","name":"Howard L. Kaufman","route":"/people/howard-kaufman/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}]}}