Hyperprogressive Disease in Anorectal Melanoma Treated by PD-1 Inhibitors

Faure, M; Rochigneux, Philippe; Olive, Daniel; Taix, Sébastien; Brenot-Rossi, I.; Gilabert, Marine

doi:10.3389/fimmu.2018.00797

Cited by 34 publications

(33 citation statements)

References 20 publications

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“…[27]. Later, an anorectal melanoma patient with hyperprogressive disease under anti-PD-1 therapy was reported [26]. In this second case, however, no information was provided on MDM2/4 or EGFR amplification.…”

Section: Introductionmentioning

confidence: 93%

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MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma

Forschner¹,

Hilke

Bonzheim

et al. 2020

Cancers

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Background: Mucosal and acral melanoma respond worse to immune checkpoint inhibitors (ICI) than cutaneous melanoma. MDM2/4 as well as EGFR amplifications are supposed to be associated with hyperprogression on ICI in diverse cancers. We therefore investigated the response of metastatic acral and mucosal melanoma to ICI in regard to MDM2/4 or EGFR amplifications and melanoma type. Methods: We conducted a query of our melanoma registry, looking for patients with metastatic acral or mucosal melanoma treated by ICI. Whole exome sequencing, FISH and immunohistochemistry on melanoma tissue could be performed on 45 of the total cohort of 51 patients. Data were correlated with patients' responses to ICI and survival. Results: 22 out of 51 patients had hyperprogressive disease (an increase in tumor load of >50% at the first staging). Hyperprogression occurred more often in case of MDM2/4 or EGFR amplification or <1% PD-L1 positive tumor cells. Nevertheless, this association was not significant. Interestingly, the anorectal melanoma type and the presence of liver metastases were significantly associated with worse survival. Conclusions: So far, we found no reliable predictive marker for patients who develop hyperprogression on ICI, specifically with regard to MDM2/4 or EGFR amplifications. Nevertheless, patients with anorectal melanoma, liver metastases or melanoma with amplified MYC seem to have an increased risk of not benefitting from ICI.

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Section: Introductionmentioning

confidence: 93%

“…Not all of these criteria were always met, such as when authors dealt with the term "hyperprogression". In some case series, staging intervals of three months and more were also included and progression speed was not always calculable [25,26].…”

Section: Introductionmentioning

confidence: 99%

MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma

Forschner¹,

Hilke

Bonzheim

et al. 2020

Cancers

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“…83 This situation has also been noted anecdotally in melanoma. 84 While the mechanism of this hyperprogressive response to presumed anticancer agents remains unclear, the proposed model suggests a number of testable hypotheses that are concordant with an initial suggestion that activation of the microenvironmental tumor associated macrophages contribute to this perverse outcome. 85 This would represent yet another mechanism for escape from treatments.…”

Section: Avoidance Of the Micrometastasesmentioning

confidence: 76%

The great escape: How metastases of melanoma, and other carcinomas, avoid elimination

Wells

Clark

Bradshaw

et al. 2018

Exp Biol Med (Maywood)

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Cancer mortality ensues from metastatic growths. Cancers use two strategies to allow for this unrelenting expansion. The first way is that early metastases are often cryptic or dormant, being invisible to both innate suppressive actions and undetected clinically. Second, both the micrometastases and later clinically lethal growths are resistant to therapies, whether standard chemotherapies, targeted biologics, or even immunotherapies. These two modes of resistance necessitate new approaches to treatments if we are to eliminate mortality from solid tumors. However, to develop such therapeutic strategies, we first need to better understand the cellular behaviors and molecular events that enable the resistances. Herein, we present a comprehensive model of changing methods of avoidance and resistance that occur during tumor progression, and doubly confound treatment by mixing survival strategies throughout the continuum creating moving targets. Melanoma is presented as the model cancer, as it is being targeted by all three types of agents for disseminated disease, with breast and prostate cancer as two other key carcinomas. Impact statement Cancers kill mainly because metastatic disease is resistant to systemic therapies. It was hoped that newer targeted and immunomodulatory interventions could overcome these issues. However, recent findings point to a generalized resistance to elimination imparted by both cancer-intrinsic and -extrinsic changes to provide survival advantages to the disseminated tumor cells. Here, we present a novel conceptual framework for the microenvironmental inputs and changes that contribute to this generalized therapeutic resistance. In addition we address the issues of experimental systems in terms of studying this phenomenon with their advantages and limitations. This is meant to spur studies into this critical aspect of tumor progression that directly leads to cancer mortality.

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“…In some case reports, patients rapidly declined and died without any subsequent therapy . A case report detailing post‐pembrolizumab hyperprogression in an anorectal melanoma patient reported that the patient received one cycle of dacarbazine without clinical improvement . In fact, most of the studies thus far recommend avoiding future immunotherapy use altogether in this subgroup given the risks of hyperprogression.…”

Section: Discussionmentioning

confidence: 99%

Hyperprogression after one dose of nivolumab in sinonasal cancer: A case report

Xiang

Minja

et al. 2019

The Laryngoscope

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In head and neck squamous cell carcinoma, immune checkpoint inhibitors (ICI) lead to improved outcomes. There has been reports of accelerated disease progression, or hyperprogression, after ICI initiation. We present a case of hyperprogression after one dose of nivolumab in maxillary sinus squamous cell carcinoma. The patient had complete vision loss due to disease progression into the orbit, as well as intracranial invasion, lytic metastases, and new widespread distal metastases. Hyperprogression can occur after the first dose of immunotherapy. Absent biomarkers regarding individual risk of hyperprogression, caution should be exercised in using ICI in sinonasal cancers with orbital abutting disease. Laryngoscope, 130:907–910, 2020

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Hyperprogressive Disease in Anorectal Melanoma Treated by PD-1 Inhibitors

Cited by 34 publications

References 20 publications

MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma

MDM2, MDM4 and EGFR Amplifications and Hyperprogression in Metastatic Acral and Mucosal Melanoma

The great escape: How metastases of melanoma, and other carcinomas, avoid elimination

Hyperprogression after one dose of nivolumab in sinonasal cancer: A case report

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