Abstract CT074: Non-comparative, open-label, multiple cohort, phase 1/2 study to evaluate nivolumab (NIVO) in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in Merkel cell carcinoma (MCC)

Topalian, Suzanne L.; Bhatia, Shailender; Hollebecque, Antoine; Awada, Ahmad; Boer, Jan Paul de; Kudchadkar, Ragini R.; Gonçalvès, Anthony; Delord, Jean‐Pierre; Martens, Uwe M.; Picazo, J.M. Lopez; Oaknin, Ana; Spanos, William C.; Aljumaily, Raid; Sharfman, William H.; Rao, Shangbang; Soumaoro, Ibrahima; Cao, Alexander; Nghiem, Paul; Schadendorf, Dirk

doi:10.1158/1538-7445.am2017-ct074

Cited by 130 publications

(135 citation statements)

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“…Only around half of patients with advanced-stage MCC respond to immune-checkpoint blockade 104,136,137 . Moreover, even during the very short follow-up period of the reported immunotherapy trials, a substantial number of patients developed acquired resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, three phase II open-label clinical trials of therapeutic antibodies against PD1 or PDL1 have demonstrated high and durable response rates 104,136,137 (TABLE 2) that are more durable than those reported in historical data of patients treated with chemotherapy. In the first study to report immune-checkpoint blockade using the anti-PD1 antibody pembrolizumab in patients with advanced-stage MCC, the response rate was 56% 136 .…”

Section: Managementmentioning

confidence: 99%

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Merkel cell carcinoma

Becker

Stang

DeCaprio

et al. 2017

Nat Rev Dis Primers

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444

565

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Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer with neuroendocrine features. MCC pathogenesis is associated with either the presence of Merkel cell polyomavirus or chronic exposure to ultraviolet light (UV), which can cause a characteristic pattern of multiple DNA mutations. Notably, in the Northern hemisphere, the majority of MCC cases are of viral aetiology; by contrast, in areas with high UV exposure, UV-mediated carcinogenesis is predominant. The two aetiologies share similar clinical, histopathological and prognostic characteristics. MCC presents with a solitary cutaneous or subcutaneous nodule, most frequently in sun-exposed areas. In fact, UV exposure is probably involved in both viral-mediated and non-viral-mediated carcinogenesis, by contributing to immunosuppression or DNA damage, respectively. Confirmation of diagnosis relies on analyses of histological features and immunological marker expression profiles of the lesion. At primary diagnosis, loco-regional metastases are already present in ~30% of patients. Excision of the tumour is the first-line therapy; if not feasible, radiotherapy can often effectively control the disease. Chemotherapy was the only alternative in advanced-stage or refractory MCC until several clinical trials demonstrated the efficacy of immune-checkpoint inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Managementmentioning

confidence: 99%

Merkel cell carcinoma

Becker

Stang

DeCaprio

et al. 2017

Nat Rev Dis Primers

Self Cite

444

565

View full text Add to dashboard Cite

show abstract

“…Nivolumab, another humanized IgG4 antibody against PD‐1, has demonstrated similar results to pembrolizumab, with an ORR of 68%, and 87% of participants maintaining their response at 6‐month follow‐up . A phase I/II trial of nivolumab combination therapies in virus‐associated tumors is ongoing (NCT02488759).…”

Section: Discussionmentioning

confidence: 97%

Molecular and immune targets for Merkel cell carcinoma therapy and prevention

Cohen

Tsai

2019

Molecular Carcinogenesis

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Merkel cell carcinoma (MCC) is a rare neuroendocrine carcinoma of the skin, for which the exact mechanisms of carcinogenesis remain unknown. Therapeutic options for this highly aggressive malignancy have historically been limited in both their initial response and response durability. Recent improvements in our understanding of MCC tumor biology have expanded therapeutic options for these patients, namely through the use of immunotherapies such as immune checkpoint inhibitors. Further elucidation of the tumor mutational landscape has identified molecular targets for therapies, which have demonstrated success in other cancer types. In this review, we discuss both current and investigational immune and molecular targets of therapy for MCC.

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“…Immune checkpoint inhibitors are another treatment option for MCC. Two monoclonal antibodies against programmed cell death 1 have been investigated as first‐line treatments for patients with advanced MCC, including nivolumab for patients with stage II–IV MCC and pembrolizumab for patients with stage IIIB–IV MCC . First‐ and second‐line avelumab treatments have demonstrated great efficacy in patients with stage IV metastatic MCC .…”

Section: Discussionmentioning

confidence: 99%

In‐transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab

Kiyohara

Shijimaya

Miyamoto

et al. 2019

The Journal of Dermatology

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A 65‐year‐old Japanese man presented with a dome‐shaped nodule, the base of which was contiguous with a dull brown plaque, on the left leg. After local excision of the cutaneous lesion and left inguinal lymph node dissection, several dermal and subcutaneous nodules developed successively on the left lower extremity. Hematoxylin–eosin staining of the primary cutaneous lesion demonstrated uniform neoplastic cells arranged in a trabecular pattern extending from the dermis to subcutis. Mitotic figures were abundant. Although the overlying epidermis was substantially intact, the Merkel cells had invaded the epidermis, resulting in Pautrier‐like microabscesses. The hyperplastic epidermis adjacent to the nodule consisted of abnormally growing atypical keratinocytes. The enlarged left inguinal lymph node and successive secondary nodules contained Merkel cells similar to those in the primary nodule. Immunohistochemically, most tumor cells were positive for CAM5.2, synaptophysin, chromogranin A, CD56 and vimentin. The tumor cells in the left inguinal lymph node were positive for CAM5.2, synaptophysin and cytokeratin 20 but negative for CM2B4, and less than 1% of the cells expressed programmed cell death ligand 1. The patient was treated with avelumab, which showed significant efficacy against the in‐transit recurrence. Two months later, all nodules had disappeared completely. We describe a case of in‐transit recurrence of Merkel cell carcinoma that was associated histologically with Bowen's disease and was successfully treated with avelumab. Although accumulation of additional cases is needed, avelumab therapy may be a useful treatment for in‐transit recurrence of Merkel cell carcinoma.

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Abstract CT074: Non-comparative, open-label, multiple cohort, phase 1/2 study to evaluate nivolumab (NIVO) in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in Merkel cell carcinoma (MCC)

Cited by 130 publications

References 0 publications

Merkel cell carcinoma

Merkel cell carcinoma

Molecular and immune targets for Merkel cell carcinoma therapy and prevention

In‐transit recurrence of Merkel cell carcinoma associated with Bowen's disease: The first reported case successfully treated by avelumab

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