Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Nov 16:9:7081-7093.
doi: 10.2147/OTT.S115245. eCollection 2016.

Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

Kevin J Harrington  1 , Robert Hi Andtbacka  2 , Frances Collichio  3 , Gerald Downey  4 , Lisa Chen  5 , Zsolt Szabo  6 , Howard L Kaufman  7
Affiliations

Efficacy and safety of talimogene laherparepvec versus granulocyte-macrophage colony-stimulating factor in patients with stage IIIB/C and IVM1a melanoma: subanalysis of the Phase III OPTiM trial

Kevin J Harrington et al. Onco Targets Ther. .

Abstract

Objectives: Talimogene laherparepvec is the first oncolytic immunotherapy to receive approval in Europe, the USA and Australia. In the randomized, open-label Phase III OPTiM trial (NCT00769704), talimogene laherparepvec significantly improved durable response rate (DRR) versus granulocyte-macrophage colony-stimulating factor (GM-CSF) in 436 patients with unresectable stage IIIB-IVM1c melanoma. The median overall survival (OS) was longer versus GM-CSF in patients with earlier-stage melanoma (IIIB-IVM1a). Here, we report a detailed subgroup analysis of the OPTiM study in patients with IIIB-IVM1a disease.

Patients and methods: The patients were randomized (2:1 ratio) to intralesional talimogene laherparepvec or subcutaneous GM-CSF and were evaluated for DRR, overall response rate (ORR), OS, safety, benefit-risk and numbers needed to treat. Descriptive statistics were used for subgroup comparisons.

Results: Among 249 evaluated patients with stage IIIB-IVM1a melanoma, DRR was higher with talimogene laherparepvec compared with GM-CSF (25.2% versus 1.2%; P<0.0001). ORR was also higher in the talimogene laherparepvec arm (40.5% versus 2.3%; P<0.0001), and 27 patients in the talimogene laherparepvec arm had a complete response, compared with none in GM-CSF-treated patients. The incidence rates of exposure-adjusted adverse events (AE) and serious AEs were similar with both treatments.

Conclusion: The subgroup of patients with stage IIIB, IIIC and IVM1a melanoma (57.1% of the OPTiM intent-to-treat population) derived greater benefit in DRR and ORR from talimogene laherparepvec compared with GM-CSF. Talimogene laherparepvec was well tolerated.

Keywords: benefit–risk; clinical trial; durable response rate; immunotherapy; oncolytic virus; talimogene laherparepvec.

PubMed Disclaimer

Conflict of interest statement

Kevin J Harrington discloses membership of scientific advisory boards for Amgen, AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer and Viralytics and discloses a consulting role with Amgen, AstraZeneca, Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer and Viralytics. Kevin J Harrington acknowledges support from the The Institute of Cancer Research/The Royal Marsden Hospital NIHR Biomedical Research Centre. Robert HI Andtbacka discloses a consulting role with Amgen. Frances Collichio discloses a consulting role with Amgen; the University of North Carolina School of Medicine receives clinical trials funding from Amgen. Gerald Downey, Lisa Chen and Zsolt Szabo are employees of Amgen. Howard L Kaufman discloses membership of scientific advisory boards for Alkermes, Amgen, EMD Serono, Merck, Prometheus and Sanofi and involvement in a speaker’s bureau for Merck. The authors report no other conflicts of interest in this work.

Figures

Figure 1
Figure 1
Patient disposition for the stage IIIB/C, IVM1a OPTiM subpopulation. Notes: aTalimogene laherparepvec was administered intralesionally ≤4 mL ×106 pfu/mL once and, after 3 weeks, ≥4 mL ×108 pfu/mL every 2 weeks. bGM-CSF was administered 125 µg/m2 subcutaneously for 14 days in 4-week cycles. Abbreviations: AE, adverse event; CI, confidence interval; CR, complete response; GM-CSF, granulocyte-macrophage colony-stimulating factor; NNTB, number needed to treat to achieve a benefit; NNTH, number needed to treat to experience a harm; PR, partial response; T-VEC, talimogene laherparepvec.
Figure 2
Figure 2
Improvement in HRQoL assessed by FACT-BRM during treatment with talimogene laherparepvec and GM-CSF in the stage IIIB/C or IVM1a OPTiM subpopulation (ITT).a Notes: aScores from unscheduled visits were not included. A patient is considered evaluable for a domain if baseline score is not the best score, there is room for evaluable improvement and there is at least one post-baseline score. TOI and total improvements are defined as ≥5-point score increase from baseline with a ≥1 cycle duration. HRQoL, pain and work improvements are defined as ≥1-point score increase from baseline with a ≥1 cycle duration. All other subscales are based on a ≥2-point score increase from baseline with a ≥1 cycle duration. Abbreviations: CI, confidence interval; FACT-BRM, Functional Assessment of Cancer Therapy-Biologic Response Modifier; GM-CSF, granulocyte-macrophage colony-stimulating factor; HRQoL, health-related quality of life; TOI, trial outcome index; T-VEC, talimogene laherparepvec.
Figure 3
Figure 3
Benefit–risk analysis. (A) Benefits by 18 months; (B) Risks by 18 months for the stage IIIB/C or IVM1a OPTiM subpopulation. Notes: Immune-mediated events occurring with talimogene laherparepvec in the stage IIIB/C or IVM1a OPTiM subpopulation included glomerulonephritis/renal papillary necrosis (grade 2), glomerulonephritis/renal failure (grade 3), vasculitis (grade 2), pneumonitis (two episodes in one patient; grades 2 and 3) and psoriasis (two episodes in one patient; grades 1 and 3). Vitiligo also occurred in 12 (7%) patients; all of these events were non-serious. Abbreviations: CI, confidence interval; GM-CSF, granulocyte-macrophage colony-stimulating factor; NNTB, number needed to treat to achieve a benefit; NNTH, number needed to treat to experience a harm; T-VEC, talimogene laherparepvec.
See this image and copyright information in PMC

References

    1. Workenhe ST, Mossman KL. Oncolytic virotherapy and immunogenic cancer cell death: sharpening the sword for improved cancer treatment strategies. Mol Ther. 2014;22(2):251–256. - PMC - PubMed
    1. Chiocca EA, Rabkin SD. Oncolytic viruses and their application to cancer immunotherapy. Cancer Immunol Res. 2014;2(4):295–300. - PMC - PubMed
    1. United States Food and Drug Administration [webpage on the Internet] Food and Drug Administration (FDA) Approves First-of-Its-Kind Product for the Treatment of Melanoma. 2015. [Accessed December 1, 2015]. Available from: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm469571.htm.
    1. European Medicines Agency The Committee for Medicinal Products for Human Use (CHMP) Summary of Opinion for Imlygic. 2015. [Accessed December 1, 2015]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Summary_of_opinion_....
    1. Ledford H. Cancer-fighting viruses win approval. Nature. 2015;526(7575):622–623. - PubMed