High response rates for T‐VEC in early metastatic melanoma (stage IIIB/C‐IVM1a)

Franke, Viola; Berger, Danique M.S.; Klop, W. Martin C.; Hiel, Bernies van der; Wiel, Bart A. van de; Meulen, Sylvia ter; Wouters, Michel W. J. M.; Houdt, Winan J. van; Akkooi, Alexander C. J. van

doi:10.1002/ijc.32172

Cited by 79 publications

(55 citation statements)

References 13 publications

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“…Franke et al from The Netherlands reported a single‐institution experience with T‐VEC monotherapy . In this study, 26 patients with stage IIIB–IVM1a melanoma treated with T‐VEC were included, with a follow‐up time ≥ 6 months.…”

Section: Real‐world Experiences With T‐vec In the Treatment Of Melanomamentioning

confidence: 99%

Intratumoral Immunotherapy—Update 2019

2019

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Intratumoral immunotherapies aim to trigger local and systemic immunologic responses via direct injection of immunostimulatory agents with the goal of tumor cell lysis, followed by release of tumor‐derived antigens and subsequent activation of tumor‐specific effector T cells. In 2019, a multitude of intratumoral immunotherapies with varied mechanisms of action, including nononcolytic viral therapies such as PV‐10 and toll‐like receptor 9 agonists and oncolytic viral therapies such as CAVATAK, Pexa‐Vec, and HF10, have been extensively evaluated in clinical trials and demonstrated promising antitumor activity with tolerable toxicities in melanoma and other solid tumor types. Talimogene laherparepvec (T‐VEC), a genetically modified herpes simplex virus type 1–based oncolytic immunotherapy, is the first oncolytic virus approved by the U.S. Food and Drug Administration for the treatment of unresectable melanoma recurrent after initial surgery. In patients with unresectable metastatic melanoma, T‐VEC demonstrated a superior durable response rate (continuous complete response or partial response lasting ≥6 months) over subcutaneous GM‐CSF (16.3% vs. 2.1%; p < .001). Responses were seen in both injected and uninjected lesions including visceral lesions, suggesting a systemic antitumor response. When combined with immune checkpoint inhibitors, T‐VEC significantly improved response rates compared with single agent; similar results were seen with combinations of checkpoint inhibitors and other intratumoral therapies such as CAVATAK, HF10, and TLR9 agonists. In this review, we highlight recent results from clinical trials of key intratumoral immunotherapies that are being evaluated in the clinic, with a focus on T‐VEC in the treatment of advanced melanoma as a model for future solid tumor indications. Implications for Practice This review provides oncologists with the latest information on the development of key intratumoral immunotherapies, particularly oncolytic viruses. Currently, T‐VEC is the only U.S. Food and Drug Administration (FDA)‐approved oncolytic immunotherapy. This article highlights the efficacy and safety data from clinical trials of T‐VEC both as monotherapy and in combination with immune checkpoint inhibitors. This review summarizes current knowledge on intratumoral therapies, a novel modality with increased utility in cancer treatment, and T‐VEC, the only U.S. FDA‐approved oncolytic viral therapy, for medical oncologists. This review evaluates approaches to incorporate T‐VEC into daily practice to offer the possibility of response in selected melanoma patients with manageable adverse events as compared with other available immunotherapies.

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Section: Real‐world Experiences With T‐vec In the Treatment Of Melanomamentioning

confidence: 99%

Intratumoral Immunotherapy—Update 2019

2019

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“…A current study based on a prospectively maintained database from the Netherlands Cancer Institute showed high complete and overall response rates in 26 stage IIIB/C in-transit melanoma patients. Twentythree patients were treatment-naïve [16]. The COSMUS-1 study investigated T-VEC treatment in the clinical practice setting in 78 patients in the USA, including 43.4% patients who received checkpoint inhibitors before T-VEC treatment or in combination and 30 patients with tumor stage IVM1b/c disease [17].…”

Section: Discussionmentioning

confidence: 99%

“…A recent multicenter chart review analyzed data from 27 patients treated with T-VEC in routine clinical practice in Germany [15]. In a current study by the Netherlands Cancer Institute, data from 26 T-VEC treated patients were analyzed based on a prospectively maintained database [16]. Recently, a real-world data study (COSMUS-1) comprising 76 patients in the USA has been published [17].…”

Section: Introductionmentioning

confidence: 99%

Talimogene laherparepvec treatment to overcome loco-regional acquired resistance to immune checkpoint blockade in tumor stage IIIB–IV M1c melanoma patients

Fröhlich

Niebel

Fietz

et al. 2020

Cancer Immunol Immunother

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Background Resistance to immune checkpoint blockade and targeted therapy in melanoma patients is currently one of the major clinical challenges. With the approval of talimogene laherparepvec (T-VEC), oncolytic viruses are now in clinical practice for locally advanced or non-resectable melanoma. Here, we describe the usage of T-VEC in stage IVM1b-M1c melanoma patients, who achieved complete remission or stable disease upon systemic treatment but suffered from a locoregional recurrence. To our knowledge, there are no case reports so far describing T-VEC as a means to overcome acquired resistance to immune checkpoint blockade or targeted therapy. Methods All melanoma patients in our department treated with T-VEC in the period of 2016-2018 were evaluated retrospectively. Data on clinicopathological characteristics, treatment response, and toxicity were analyzed. Results Fourteen melanoma patients were treated with T-VEC in our center. Six patients (43%) received T-VEC first-line. In eight patients (57%), T-VEC followed a prior systemic therapy. Three patients with M1b stage and one patient with M1c stage melanoma were treated with T-VEC. These patients suffered from loco-regional progress, whilst distant metastases had regressed during prior systemic treatment. 64% of patients showed a benefit from therapy with T-VEC. The durable response rate was 36%. Conclusion T-VEC represents an effective and tolerable treatment option. This is true not only for loco-regionally advanced melanoma patients, but also for patients with stable or regressive systemic metastases who develop loco-regionally acquired resistance upon treatment with immune checkpoint blockade or targeted therapy. A sensible selection of suitable patients seems to be crucial.

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“…The herpes virus vaccine called T-VEC, engineered to selectively replicate in tumour cells and to secrete GM-CSF, has been approved by the FDA for intratumoural administration for stage IIIB/C-IV melanoma based on the phase 3 OPTiM trial [51,157], as mentioned above (see Section 2.2.1). A recently reported series of off-trial uses of T-VEC in early advanced melanoma (stages IIIB/C-IVM1a) showed a CR rate of 61.5% and a PR rate of 26.9, with a DCR of 92.3% [158].…”

Section: Oncolytic Virus Vaccinesmentioning

confidence: 96%

Cancer Vaccines

Henriquez¹,

Arkenau²,

Dutoit³

et al. 2019

Cancer Immunotherapy and Biological Cancer Treatments

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Recent advances in immuno-oncology have allowed for the design of more specific and efficient cancer vaccine approaches. There has been an improvement in molecular biology techniques, as well as a greater understanding of the mechanisms involved in the activation and regulation of T cells and the interplay between the components of the immune system and the escape mechanisms used by cancer cells and the tumour microenvironment. As a result, many interesting developments in therapeutic cancer vaccines are ongoing, with influence on survival still to be proven. The spectrum of tumour antigens that are recognised by T cells is still largely unchartered and, most importantly, dynamically evolving over time, driven by clonal evolution and treatment-driven selection. Vaccine approaches currently in development and tested in clinical studies are based on tumour antigens specifically identified for each tumour type, on tumour cells or dendritic cells, the latter having the potential to be modified to incorporate immunostimulatory genes. However, interplay between the immune system and the tumour and the inhibitory mechanisms developed by tumour cells to subvert immune responses are crucial issues that will need to be targeted in order for efficient therapeutic vaccines to emerge.

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High response rates for T‐VEC in early metastatic melanoma (stage IIIB/C‐IVM1a)

Cited by 79 publications

References 13 publications

Intratumoral Immunotherapy—Update 2019

Intratumoral Immunotherapy—Update 2019

Talimogene laherparepvec treatment to overcome loco-regional acquired resistance to immune checkpoint blockade in tumor stage IIIB–IV M1c melanoma patients

Cancer Vaccines

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