A phase II randomized trial of talimogene laherparepvec oncolytic immunotherapy with or without radiotherapy for patients with cutaneous metastases from solid tumors Journal Article

   

Authors:	Barker, C. A.; D'Angelo, S. P.; Wasilewski, G.; Steckler, A. M.; Lian, M.; Zhang, Z.; Chapman, P. B.; Shoushtari, A. N.; Ariyan, C. E.
Article Title:	A phase II randomized trial of talimogene laherparepvec oncolytic immunotherapy with or without radiotherapy for patients with cutaneous metastases from solid tumors
Abstract:	Background: Cutaneous metastases (CMs) are a manifestation of advanced cancer and can be treated with oncolytic immunotherapy. Laboratory studies suggest radiotherapy (RT) may facilitate response to immunotherapy. We hypothesized that oncolytic immunotherapy with talimogene lapherparepvec (T-VEC, an oncolytic immunotherapy that expresses granulocyte–macrophage colony stimulating factor) and RT would produce response in non-targeted metastases. Methods: A randomized phase 2 trial of T-VEC+/-RT was conducted. Eligible patients had ≥1 CM from a solid tumor amenable to T-VEC and RT and another measurable metastasis. Tumor and overall response was assessed using modified World Health Organization (mWHO) criteria. Adverse events (AEs) and quality of life (QOL) were characterized using CTCAE v4.0 and Skindex-16, respectively. Correlative analyses of tumor genomics and the immune system were performed. Results: 19 patients were randomized to receive T-VEC (n = 9) or T-VEC+RT (n = 10). One patient in each arm demonstrated complete response in the largest non-targeted metastasis. The trial was closed after the first stage of enrollment because of no overall mWHO responses, slow accrual and the COVID-19 pandemic. AEs were consistent with prior reports of T-VEC. Skin related QOL was poor before and after treatment. Median progression free survival was 1.2 and 2.5 months in the T-VEC and T-VEC+RT arms; median overall survival was 4.9 and 17.3 months in the T-VEC and T-VEC+RT arms. Analyses of peripheral blood cells and cytokines demonstrated responders exhibited several outlying lymphocyte and cytokine parameters. Conclusions: Low overall response rate, slow accrual, and the COVID-19 pandemic led to closure of this trial. Responses in non-injected and non-irradiated metastases were infrequent. © 2024 Elsevier B.V.
Keywords:	adult; cancer survival; controlled study; treatment response; aged; major clinical study; overall survival; solid tumor; cancer patient; cancer radiotherapy; cancer immunotherapy; progression free survival; quality of life; phase 2 clinical trial; randomized controlled trial; radiotherapy; immunotherapy; radiation therapy; lymphocyte; skin metastasis; overall response rate; cutaneous metastases; talimogene laherparepvec; human; male; female; article; cutaneous metastasis; oncogenomics; t-vec; tvec; coronavirus disease 2019; skindex-16; oncolytic immunotherapy; viral immunotherapy
Journal Title:	Radiotherapy and Oncology
Volume:	200
ISSN:	0167-8140
Publisher:	Elsevier Inc.
Date Published:	2024-11-01
Start Page:	110478
Language:	English
DOI:	10.1016/j.radonc.2024.110478
PUBMED:	39159678
PROVIDER:	scopus
PMCID:	PMC11438562
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85201716236&doi=10.1016%2fj.radonc.2024.110478&partnerID=40&md5=1d45cbeb2d4a4e77b128eb5fdaf87c06
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK author is Christopher A. Barker -- Source: Scopus

https://synapse.mskcc.org/synapse/works/has_related_data_chk/218204