Intralesional bevacizumab in patients with Human immunodeficiency virus–associated Kaposi's sarcoma in the upper airway

Ablanedo-Terrazas, Yuria; Barrera, Claudia Alvarado-de la; Ormsby, Christopher E.; Ruiz-Cruz, Matilde; Reyes‐Terán, Gustavo

doi:10.1002/lary.24988

Cited by 15 publications

(11 citation statements)

References 30 publications

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“…In an open-label phase 2 study, 14 PWH with KS in the upper airway were randomized 1:1 to ART alone versus ART and intralesional bevacizumab. No difference in tumor response was observed between these two groups 113…”

Section: Discussionmentioning

confidence: 80%

Cancer Immunotherapy in Adult Patients with HIV

Khalaf

Dandachi

Granwehr

et al. 2022

Journal of Investigative Medicine

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The availability of antiretroviral therapy (ART) has increased the life expectancy of people with HIV (PWH) and reduced the incidence of AIDS-associated malignancies, yet PWH have a significantly increased incidence of malignancy and less favorable outcomes of cancer treatment compared with the general population.Immunotherapy has revolutionized cancer therapy, becoming the standard of care for various malignancy treatments. However, PWH are an underserved population with limited access to clinical trials and cancer treatment.This review of the available evidence on different classes of cancer immunotherapy in PWH is mostly based on case reports, case series, but few prospective studies and clinical trials due to the exclusion of PWH from most oncologic clinical trials. The results of the available evidence support the safety of immunotherapy in PWH. Immunotherapy has similar effectiveness in PWH, an acceptable toxicity profile, and has no clinically significant impact on HIV viral load and CD4-T cell count. In addition, there is no reported change in the incidence of opportunistic infections and other complications for PWH with well-controlled viremia.This review aims to briefly summarize the current state of immunotherapy in cancer, guide clinicians in the management of immunotherapy in cancer PWH, and encourage the inclusion of PWH in clinical trials of cancer immunotherapy.

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Section: Discussionmentioning

confidence: 80%

Cancer Immunotherapy in Adult Patients with HIV

Khalaf

Dandachi

Granwehr

et al. 2022

Journal of Investigative Medicine

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“…Lack of tumor penetration has been proposed as one reason for the limited and highly variable efficacy of bevacizumab in KS. Even when directly injected into upper-respiratory KS lesions, bevacizumab, though well-tolerated, had no effect on tumor size compared to the control group [32]. This is demonstrative of the limitations of whole-antibody anti-VEGF therapy on vascular tumors and motivated our exploration of antibody fragments.…”

Section: Introductionmentioning

confidence: 93%

DLX1008 (brolucizumab), a single-chain anti-VEGF-A antibody fragment with low picomolar affinity, leads to tumor involution in an in vivo model of Kaposi Sarcoma

et al. 2020

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Kaposi Sarcoma (KS) is among the most angiogenic cancers in humans and an AIDS-defining condition. KS-associated herpesvirus (KSHV) is necessary for KS development, as is vascular endothelial growth factor (VEGF-A). DLX1008 is a novel anti-VEGF-A antibody single-chain variable fragment (scFv) with low picomolar affinity for VEGF-A. In vivo imaging techniques were used to establish the efficacy of DLX1008 and to establish the mechanism of action; this included non-invasive imaging by ultrasound and optical fluorescence, verified by post-mortem histochemistry. The results showed that DLX1008 was efficacious in a KS mouse model. The NSG mouse xenografts suffered massive internal necrosis or involution, consistent with a lack of blood supply. We found that imaging by ultrasound was superior to external caliper measurements in the validation of the angiogenesis inhibitor DLX1008. Further development of DLX1008 against VEGF-dependent sarcomas is warranted.

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“…In 2012, a phase II study evaluated the effect of this drug in 17 PLWH with KS persistence or progression despite cART introduction and reported a 31% complete or partial response at 8 months [88]. However, another randomized study on 14 patients failed to show a significant effect of intralesional bevacizumab in upper airways KS lesions [89]. Another single-chain anti-VEGF-A antibody fragment, brolucizumab, approved for the treatment of neovascular age-related macular degeneration, was tested in a mice model of KS with significant tumor regression [96].…”

Section: Anti-angiogenic Therapies In Ks Treatmentmentioning

confidence: 99%

Therapeutic Perspectives in the Systemic Treatment of Kaposi’s Sarcoma

Valantin

Royston

Hentzien³

et al. 2022

Cancers

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In patients with Kaposi’s sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects.

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Intralesional bevacizumab in patients with Human immunodeficiency virus–associated Kaposi's sarcoma in the upper airway

Abstract: Intralesional administration of bevacizumab was well tolerated but had no impact on upper respiratory tract Kaposi's sarcoma lesions of HIV-infected patients.

Cited by 15 publications

References 30 publications

Cancer Immunotherapy in Adult Patients with HIV

Cancer Immunotherapy in Adult Patients with HIV

DLX1008 (brolucizumab), a single-chain anti-VEGF-A antibody fragment with low picomolar affinity, leads to tumor involution in an in vivo model of Kaposi Sarcoma

Therapeutic Perspectives in the Systemic Treatment of Kaposi’s Sarcoma

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